Browsing by Author "Grosskurth, Heiner"

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    Alcohol use, Mycoplasma genitalium and other STIs associated with HIV incidence among women at high risk in Kampala, Uganda
    (Journal of acquired immune deficiency syndromes, 2013) Vandepitte, Judith; Weiss, Helen A.; Bukenya, Justine; Nakubulwa, Susan; Mayanja, Yunia; Matovu, Godfrey; Kyakuwa, Nassim; Hughes, Peter; Hayes, Richard; Grosskurth, Heiner
    In 2008, the first clinic for women involved in high risk sexual behaviour was established in Kampala, offering targeted HIV prevention. This paper describes rates, determinants and trends of HIV incidence over 3 years. Methods—1027 women at high risk were enrolled into a closed cohort. At 3-monthly visits, data were collected on socio-demographic variables and risk behaviour; biological samples were tested for HIV and other STIs. Hazard ratios (HR) for HIV incidence were estimated using Cox proportional hazards regression, among the 646 women HIV negative at enrolment. Results—HIV incidence was 3.66/100pyr and declined from 6.80/100pyr in the first calendar year to 2.24/100pyr and 2.53/100pyr in the following years (P-trend=0.003). Socio-demographic and behavioural factors independently associated with HIV incidence were younger age, younger age at first sex, alcohol use (including frequency of use and binge drinking), number of paying clients in the past month, inconsistent condom use with clients, and not being pregnant. HIV incidence was also independently associated with M. genitalium infection at enrolment (aHR=2.28, 95%CI: 1.15-4.52), and with N. gonorrhoeae (aHR=5.91, 95%CI: 3.04-11.49) and T. vaginalis infections at the most recent visit (aHR=2.72, 95%CI: 1.27-5.84). The PAF of HIV incidence for alcohol use was 63.5% (95%CI 6.5%-85.8%), and for treatable STI/RTI was 70.0% (95%CI 18.8%-87.5%). Conclusions—Alcohol use and STIs remain important risk factors for HIV acquisition, which call for more intensive control measures in women at high risk. Further longitudinal studies are needed to confirm the association between Mycoplasma genitalium and HIV acquisition.
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    Bacterial vaginosis among women at high risk for HIV in Uganda: high rate of recurrent diagnosis despite treatment
    (Sexually transmitted infections, 2016) Francis, Suzanna C.; Looker, Clare; Vandepitte, Judith; Bukenya, Justine; Mayanja, Yunia; Nakubulwa, Susan; Hughes, Peter; Hayes, Richard J.; Weiss, Helen A.; Grosskurth, Heiner
    Bacterial vaginosis (BV) is associated with increased risk for sexually transmitted infections (STIs) and HIV acquisition. This study describes the epidemiology of BV in a cohort of women at high risk for STI/HIV in Uganda over 2 years of follow-up between 2008–2011. Methods 1027 sex workers or bar workers were enrolled and asked to attend 3-monthly follow-up visits. Factors associated with prevalent BV were analysed using multivariate random-effects logistic regression. The effect of treatment on subsequent episodes of BV was evaluated with survival analysis. Results Prevalences of BV and HIV at enrolment were 56% (573/1027) and 37% (382/1027), respectively. Overall, 905 (88%) women tested positive for BV at least once in the study, over a median of four visits. Younger age, a higher number of previous sexual partners and current alcohol use were independently associated with prevalent BV. BV was associated with STIs, including HIV. Hormonal contraception and condom use were protective against BV. Among 853 treated BV cases, 72% tested positive again within 3 months. There was no difference in time to subsequent BV diagnosis between treated and untreated women. Conclusions BV was highly prevalent and persistent in this cohort despite treatment. More effective treatment strategies are urgently needed.
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    Barriers to starting ART and how they can be overcome: individual and operational factors associated with early and late start of treatment
    (Tropical medicine & international health, 2010) Parkes-Ratanshi, Rosalind; Bufumbo, Leonard; Nyanzi-Wakholi, Barbara; Levin, Jonathan; Grosskurth, Heiner; Lalloo, David G.; Kamali, Anatoli
    Despite expanding access to antiretroviral therapy (ART) in Sub-Saharan Africa, there are few data on patients’ perceptions about starting ART to explore issues affecting decisions to start ART in eligible individuals during the ART roll out. Methods We studied patterns of ART uptake for 957 participants in a trial of cryptococcal disease prevention and performed a qualitative cross-sectional study about issues affecting decisions to start ART in this cohort. In-depth interviews (IDIs) were conducted with 48 participants who started ART after variable time on the trial. results Time to starting ART from trial enrolment decreased during the ART roll out (Median 83 days to 68 days). Multiple factors causing delay to ART were reported; awaiting home visit by service provider (P = 0.025), domestic issues (P = 0.028), moving from area (P £ 0.001) and fear of side effects (P = 0.013) were statistically significant. In the IDIs, fear of side effects was the strongest factor for delay and observation of health improvement in others on ART was the strongest inducement to start. Information from patients already taking ART was the most valued source of information. Conclusions This study provided novel information about factors encouraging people to start ART early; positive beliefs about ART were the most important. Whilst side effects of ART must not be downplayed, programmes should provide information in a balanced way to prevent unnecessary fear of starting ART. Those already receiving ART were found to be good advocates and should be utilised by ART programmes to educate others.
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    A Cluster-Randomised Trial to Compare Home-Based with Health Facility- Based Antiretroviral Treatment in Uganda: Study Design and Baseline Findings
    (Bentham Science Publishers Ltd., 2007) Amuron, Barbara; Coutinho, Alex; Grosskurth, Heiner; Nabiryo, Christine; Birungi, Josephine; Namara, Geoffrey; Levin, Jonathan; Smith, Peter G.; Jaffar, Shabbar
    The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We re- port the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 10 6 cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load 100,000 copies. Baseline characteris- tics did not change over time. Considerably fewer men than women presented for treatment.
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    Cost Effectiveness Analysis of Clinically Driven versus Routine Laboratory Monitoring of Antiretroviral Therapy in Uganda and Zimbabwe
    (PloS one, 2012) Lara, Antonieta Medina; Kigozi, Jesse; Amurwon, Jovita; Muchabaiwa, Lazarus; Wakaholi, Barbara Nyanzi; Mota, Ruben E. Mujica; Walker, A. Sarah; Kasirye, Ronnie; Ssali, Francis; Reid, Andrew; Grosskurth, Heiner; Babiker, Abdel G.; Kityo, Cissy; Katabira, Elly; Munderi, Paula; Mugyenyi, Peter; Hakim, James; Darbyshire, Janet; Gibb, Diana M.; Gilks, Charles F.
    Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated.Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial.3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm3) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term.There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test.
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    Decreasing trends of bacteraemia among HIV-infected Ugandan adults: incidence, aetiology, clinical outcomes and effect of antiretroviral therapy in a semi-urban setting (2000–2008)
    (Tropical Medicine & International Health, 2011) Zawedde Muyanja, Stella; Larke, Natasha; Rutebarika, Diana; Kaddu, Ismael; Nakubulwa, Susan; Levin, Jonathan; Grosskurth, Heiner; Miiro, George
    To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV-infected Ugandans in a semi-urban setting. methods A cohort of HIV-1-infected Ugandans aged 15 or older was followed from 2000 to 2008. Clinical, haematological and immunological measurements were taken at 6-monthly visits. Additionally, patients reported to outpatient clinics whenever they were ill. Patients with elevated axillary temperature above 37.4 C consistently triggered clinical assessment (with mandatory blood cultures) and empirical management protocol. Daily cotrimoxazole prophylaxis and highly active antiretroviral therapy (HAART) were introduced stepwise to eligible patients in August 2000 and February 2003, respectively. We compared the rates of bacteraemia across five calendar periods using random-effects Poisson regression for the effect of HAART at the population level. results A total of 246 bacteraemia episodes (including multiple episodes) were documented among 188 individuals (crude incidence: 42.4 events per 1000 person-years; 95% CI: 35.0, 51.4). The most common species isolated was Streptococcus pneumoniae. After adjustment for current age, clinical characteristics at enrolment (CD4+ T-cell counts and WHO stage) and time since enrolment, the incidence of bacteraemia dropped significantly when HAART was widely available compared with the period when treatment was not available (adjusted hazard ratio: 0.17; 95% CI: 0.09, 0.35). No poor health outcomes (death or lack of clinical response to antibiotics) after bacteraemia occurred after complete access to HAART. conclusions HAART availability in a resource-poor setting substantially reduced the trends of bacteraemia among HIV-infected adults. This may further impact on future morbidity and healthcare costs of HIV-infected people.
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    High Levels of Persistent Problem Drinking in Women at High Risk for HIV in Kampala, Uganda: A Prospective Cohort Study
    (International journal of environmental research and public health, 2016) Weiss, Helen A.; Vandepitte, Judith; Bukenya, Justine N.; Mayanja, Yunia; Nakubulwa, Susan; Kamali, Anatoli; Seeley, Janet; Grosskurth, Heiner
    The aim of this study was to describe the epidemiology of problem drinking in a cohort of women at high-risk of HIV in Kampala, Uganda. Overall, 1027 women at high risk of HIV infection were followed from 2008 to 2013. The CAGE and AUDIT questionnaires were used to identify problem drinkers in the cohort. Interviewer-administered questionnaires were used to ascertain socio-demographic and behavioural factors. Blood and genital samples were tested for HIV and other sexually transmitted infections. At enrollment, most women (71%) reported using alcohol at least weekly and about a third reported having drunk alcohol daily for at least 2 weeks during the past 3 months. Over half (56%) were problem drinkers by CAGE at enrollment, and this was independently associated with vulnerability (being divorced/separated/widowed, less education, recruiting clients at bars/clubs, and forced sex at first sexual experience). Factors associated with problem drinking during follow-up included younger age, meeting clients in bars/clubs, number of clients, using drugs and HSV-2 infection. HIV prevalence was associated with drinking at enrollment, but not during follow-up. This longitudinal study found high levels of persistent problem drinking. Further research is needed to adapt and implement alcohol-focused interventions in vulnerable key populations in sub-Saharan Africa.
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    The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models
    (American journal of epidemiology, 2015) Ford, Deborah; Robins, James M.; Petersen, Maya L.; Gibb, Diana M.; Gilks, Charles F.; Mugyenyi, Peter; Grosskurth, Heiner; Hakim, James; Katabira, Elly; Babiker, Abdel G.; Walker, A. Sarah
    In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 personyears of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.
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    The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models
    (American journal of epidemiology, 2015) Ford, Deborah; Robins, James M.; Mugyenyi, Peter; Grosskurth, Heiner; Hakim, James; Katabira, Elly; Babiker, Abdel G.; Walker, A. Sarah
    In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.
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    The Impact of the AIDS Epidemic on the Lives of Older People in Rural Uganda
    (School of Development Studies, 2008) Seeley, Janet; Kabunga, Elizabeth; Tumwekwase, Grace; Wolff, Brent; Grosskurth, Heiner
    The impact of HIV and AIDS on older people (over 60) is often portrayed as bound up in the care of children who are left when their parents die. There is, however, a growing awareness that the epidemic touches older people’s lives in other ways; affecting their socio-economic situation, their own sexuality and choices about partnerships as well as affecting relationships with their remaining children and relatives. Growing old presents challenges beyond HIV and AIDS as health wanes and the ability to plan ahead and care for ones-self and any dependents decreases. It is these dimensions of older people’s lives that we explore in this paper. Using a lifecourse approach we analyse longitudinal data from studies in 1991/1992 and 2006/2007 from rural Uganda to provide a picture of daily life of four older people, describing the challenges that they face in coming to terms with a world changed by the AIDS epidemic. By focusing on the lives of four people (three widows and a widower in their late 70s/80s) we show the great importance of their socio-economic status, as well as reciprocal relationships with family and friends, in sustaining them in the remaining years of their lives.
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    Natural history of Mycoplasma genitalium Infection in a Cohort of Female Sex Workers in Kampala, Uganda
    (Sexually transmitted diseases, 2013) Vandepitte, Judith; Vandepitte, Judith; Weiss, Helen A.; Kyakuwa, Nassim; Nakubulwa, Susan; Muller, Etienne; Buvé, Anne; Van der Stuyft, Patrick; Hayes, Richard; Grosskurth, Heiner
    There have been few studies of the natural history of Mycoplasma genitalium in women. We investigated patterns of clearance and recurrence of untreated M. genitalium infection in a cohort of female sex workers in Uganda. Methods—Women diagnosed as having M. genitalium infection at enrollment were retested for the infection at 3-month intervals. Clearance of infection was defined as testing negative after having a previous positive result: persistence was defined as testing positive after a preceding positive test result, and recurrence as testing positive after a preceding negative test result. Adjusted hazard ratios for M. genitalium clearance were estimated using Cox proportional hazards regression. Results—Among 119 participants infected with M. genitalium at enrollment (prevalence, 14%), 55% had spontaneously cleared the infection within 3 months; 83%, within 6; and 93%, within 12 months. The overall clearance rate was 25.7/100 person-years (pyr; 95% confidence interval, 21.4–31.0). HIV-positive women cleared M. genitalium infection more slowly than did HIVnegative women (20.6/100 pyr vs. 31.3/100 pyr, P = 0.03). The clearance rate was slower among HIV-positive women with CD4 counts less than 350/mL3 than among those with higher CD4 counts (9.88/100 pyr vs. 29.5/100 pyr, P < 0.001). After clearing the infection, M. genitalium infection recurred in 39% women. Conclusions—M. genitalium is likely to persist and recur in the female genital tract. Because of the urogenital tract morbidity caused by the infection and the observed association with HIV acquisition, further research is needed to define screening modalities, especially in populations at high risk for HIV, and to optimize effective and affordable treatment options.
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    Parenting and money making: Sex work and women’s choices in urban Uganda
    (A Journal of Transnational Women's & Gender Studies, 2011) Zalwango, Flavia; Eriksson, Lina; Seeley, Janet; Nakamanya, Sarah; Vandepitte, Judith; Grosskurth, Heiner
    Based upon detailed life histories of 96 Ugandan sex workers, this article documents the pathways women take into prostitution through marital separation and the subsequent need to support children via rural-urban migration to obtain wage work in Kampala. The money women receive from selling sex and other work helped them to independently pay for their housing children’s school fees, and food for their family without receiving support from partners. In their narratives women portrayed themselves as mothers, wives, partners, friends and workers with self-esteem and the hope of improvement in their lives through their own efforts.
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    Performance of Commercial Herpes Simplex Virus Type-2 Antibody Tests Using SerumSamples From Sub-Saharan Africa: A Systematic Review and Meta-analysis
    (Biraro, S., Mayaud, P., Morrow, R. A., Grosskurth, H., & Weiss, H. A. (2011). Performance of commercial herpes simplex virus type-2 antibody tests using serum samples from Sub-Saharan Africa: a systematic review and meta-analysis. Sexually transmitted diseases, 140-147., 2011) Biraro, Samuel; Mayaud, Philippe; Morrow, Rhoda Ashley; Grosskurth, Heiner; Weiss, Helen A.
    Several commercial type-specific serologic tests are available for herpes simplex virus type 2 (HSV-2). Poor specificity of some tests has been reported on samples from sub-Saharan Africa. Methods: To summarize the performance of the tests using samples from sub-Saharan Africa, we conducted a systematic review of publi- cations reporting performance of commercially available HSV-2 tests against a gold standard (Western Blot or monoclonal antibody-blocking EIA). We used random-effects meta-analyses to summarize sensitivity and specificity of the 2 most commonly evaluated tests, Kalon gG2 enzyme-linked immunosorbent assay (ELISA), and Focus HerpeSelect HSV-2 ELISA. Results: We identified 10 eligible articles that included 21 studies of the performance of Focus, and 12 of Kalon. The primary analyses included studies using the manufacturers' cut-offs (index value = 1.1). Focus had high sensitivity (random effects summary estimate 99%, 95% confidence interval [CI]: 99%-100%) but low specificity (69%, 95% CI: 59%- 80%). Kalon had sensitivity of 95% (95% CI: 93%- 97%) and specificity of 91% (95% CI: 86%-95%). Specificity of Focus was significantly lower ( P = 0.002) among HIV-positive (54%, 95% CI: 40%- 68%) than HIV-negative individuals (69%, 95% CI: 56%- 82%). When the cut-off optical density index was increased above the recommended value of 1.1 to between 2.2 and 3.5, the specificity of Focus increased to 85% (95% CI: 77%-92%). Conclusions: Sensitivity and specificity of HSV-2 tests used in sub-Saharan Africa vary by setting, and are lower than reported from studies in the United States and Europe. Increasing the cut-off optical density index may improve test performance. Evaluation of test per- formance in a given setting may help deciding which test is most appropriate.
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    Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial
    (PLoS Med, 2012) Gibb, Diana M.; Kizito, Hilda; Russell, Elizabeth C.; Chidziva, Ennie; Zalwango, Eva; Nalumenya, Ruth; Spyer, Moira; Tumukunde, Dinah; Nathoo, Kusum; Munderi, Paula; Kyomugisha, Hope; Hakim, James; Grosskurth, Heiner; Gilks, Charles F.; Walker, Sarah; Musoke, Phillipa
    Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)–recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Methods and Findings: Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0–4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths ($22 wk), and 137 (35%) terminations/miscarriages (,22 wk). Of 226 live-births, seven (3%) infants died ,2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p.0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12–38) months. From mothers’ ART, 62/9/111 infants had no/20%–89%/$90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/ 182(40%) infants were breast-fed for median 94 (IQR 75–212) days. Overall, 14 infants died at median (IQR) age 9 (3–23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p.0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens. Conclusions: Overall 1-year 5% infant mortality was similar to the 2%–4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.
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    Prevalence and Correlates of Mycoplasma genitalium Infection Among Female Sex Workers in Kampala, Uganda
    (Journal of Infectious Diseases, 2012) Vandepitte, Judith; Muller, Etienne; Bukenya, Justine; Nakubulwa, Susan; Kyakuwa, Nassim; Buve, Anne; Weiss, Helen; Hayes, Richard; Grosskurth, Heiner
    The importance of Mycoplasma genitalium in human immunodeficiency virus (HIV)–burdened sub–Saharan Africa is relatively unknown. We assessed the prevalence and explored determinants of this emerging sexually transmitted infection (STI) in high-risk women in Uganda. Methods. Endocervical swabs from 1025 female sex workers in Kampala were tested for Mycoplasma genitalium using a commercial Real-TM polymerase chain reaction assay. Factors associated with prevalent Mycoplasma genitalium, including sociodemographics, reproductive history, risk behavior, and HIV and other STIs, were examined using multivariable logistic regression. Results. The prevalence of Mycoplasma genitalium was 14% and higher in HIV-positive women than in HIVnegative women (adjusted odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12–2.41). Mycoplasma genitalium infection was less prevalent in older women (adjusted OR, 0.61; 95% CI, .41–.90 for women ages 25–34 years vs ,25 years; adjusted OR, 0.32; 95% CI, .15–.71 for women $35 years vs those ,25 years) and in those who had been pregnant but never had a live birth (adjusted OR, 2.25; 95% CI, 1.04–4.88). Mycoplasma genitalium was associated with Neisseria gonorrhoeae (adjusted OR, 1.84; 95% CI, 1.13–2.98) and with Candida infection (adjusted OR, 0.41; 95% CI, .18–.91), and there was some evidence of association with Trichomonas vaginalis (adjusted OR, 1.56; 95% CI, 1.00–2.44). Conclusions. The relatively high prevalence of Mycoplasma genitalium and its association with prevalent HIV urgently calls for further research to explore the potential role this emerging STI plays in the acquisition and transmission of HIV infection.
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    The rates of HIV-1 superinfection and primary HIV-1 infection are similar in female sex workers in Uganda
    (Theoretical Medicine and Bioethics, 2008) Redd, Andrew D.; Ssemwanga, Deogratius; Vandepitte, Judith; Wendel, Sarah K.; Ndembi, Nicaise; Bukenya, Justine; Nakubulwa, Susan; Grosskurth, Heiner; Parry, Chris M.; Martens, Craig; Bruno, Daniel; Porcella, Stephen F.; Quinn, Thomas C.; Kaleebu, Pontiano
    To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers in Kampala, Uganda. Design—A retrospective analysis of individuals who participated in a clinical cohort study among high-risk female sex workers in Kampala, Uganda. Methods—Plasma samples from HIV-infected female sex workers (FSW) in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSW from the same cohort, and incidence rate ratios were compared. Results—The rate of superinfection in these women (7/85; 3.4/100py) was not significantly different from the rate of primary infection in the same population (3.7/100py; IRR=0.91, p=0.42). Seven women also entered the study dual infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (p=0.05), and trended to be older and more likely to be widowed (p=0.07). Conclusions—In this cohort of female sex workers, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar-workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.
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    Reduced morbidity and mortality in the first year after initiating highly active anti-retroviral therapy (HAART) among Ugandan adults
    (Tropical Medicine & International Health, 2009) Miiro, George; Todd, Jim; Mpendo, Juliet; Watera, Christine; Munderi, Paula; Nakubulwa, Susan; Kaddu, Ismael; Rutebarika, Diana; Grosskurth, Heiner
    To evaluate the effect of highly active anti-retroviral therapy (HAART) and cotrimoxazole prophylaxis on morbidity after HAART eligibility. methods Between 1999 and 2006, we collected morbidity data from a community-based cohort of HAART-eligible patients, comparing patients initiating HAART and those non-HAART. Patients aged 15 years or older visited the clinic every 6 months and when ill. Baseline data on patients’ characteristics, WHO stage, haemoglobin and CD4+ T-cell counts, along with follow-up data on morbidity (new, recurrent and drug-related), were collected for the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of cotrimoxazole prophylaxis by Mantel–Haenszel methods. A negative binomial regression model was used to assess rate ratios (RR) after adjustment for other confounders, including cotrimoxazole. results A total of 219 HAART patients (median age 37 years; 73% women; 82% using cotrimoxazole prophylaxis, median haemoglobin 11.7 g ⁄ dl and median CD4+ 131 cells ⁄ ll) experienced 94 events in 127 person-years. 616 non-HAART patients (median age 33 years; 70% women; 26% using cotrimoxazole prophylaxis, median haemoglobin 11.2 g ⁄ dl and median CD4+ 130 cells ⁄ ll) experienced 862 events in 474 person-years. The overall morbidity during the first year of HAART was 80% lower than among non-HAART patients (adjusted RR = 0.20, 95% CI: 0.12–0.34). Cotrimoxazole prophylaxis also reduced morbidity (adjusted RR = 0.65, 95% CI: 0.45–0.94). conclusion These results confirm the reduction in morbidity due to HAART, and the additional protection of cotrimoxazole prophylaxis.
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    Scale-up of antiretroviral therapy in sub-Saharan Africa – priorities for public health research
    (Tropical Medicine and International Health, 2007) Jaffar, Shabbar; Mbidde, Edward; Robb, Alistair; Coutinho, Alex; Muwanga, Moses; Obermeyer, Carla Makhlouf; Weller, Ian; Hart, Graham; Smith, Peter G.; Haines, Andy; Grosskurth, Heiner
    The scale-up of antiretroviral therapy (ART) in Africa is the largest health delivery programme ever contemplated on the continent. About 1.3 million people are now on ART and a further 3.5 million are estimated to be in current need of ART. Research is required urgently to identify strategies of scaling-up ART delivery to ensure that it has high coverage, is effective and is available equitably. Furthermore, the number of new infections occurring daily far outstrips the number of patients being placed on ART (World Health Organization, 2007), and to halt the expanding number eligible for treatment, a pressing priority for research is to determine ways of effectively involved in the different components of ART delivery and how should they be trained and supported? What are the costs of ART both to the health services and to the patients? integrating human immunodeficiency virus (HIV) prevention with ART delivery strategies. At present, most government-led ART programmes are based in district or tertiary-level hospitals. This limits the number who can be treated; as hospital services are overburdened, there is a severe shortage of clinical staff, especially physicians, and most hospitals are in urban settings and difficult to access by the majority of people who live in rural areas (Jaffar et al. 2005; Gilks et al. 2006). Home-based care may not be acceptable in many settings because of stigma issues, but it is being evaluated in at least one cluster randomized trial (Jaffar et al., unpublished data). Peripheral health facilities, run by nursing staff or clinical assistants, provide basic primary care in rural communities across Africa. Research is required to determine if ART could be initiated and maintained from such centres. Could the centres monitor patients for side effects from therapy? Could they make referrals to hospitals as and when appropriate? What kind of adherence support and behaviour counselling should the centres provide? How often should patients be followed up and by whom? What should be the minimum cadre of staff
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    ‘This is where we buried our sons’ : people of advanced old age coping with the impact of the AIDS epidemic in a resource-poor setting in rural Uganda
    (Ageing & Society, 2009) Seeley, Janet; Wolff, Brent; Kabunga, Elizabeth; Tumwekwase, Grace; Grosskurth, Heiner
    Much research on the impact of HIV and AIDS on older people fails to differentiate between age groups, and treats those aged from 50 years to the highest ages as homogeneous. The ‘oldest old’ or those aged over 75 years may be particularly vulnerable through declining health and independence as a result of the AIDS epidemic, which has forced some to take on roles that younger relatives would have performed had they lived. In this paper we describe the past and current experience of eight people in advanced old age living in rural Uganda who were informants for an ethnographic study of the impact of HIV and AIDS on households during 1991–92 and again in 2006–07. The aim of the study was to understand how they had coped with the impacts of the epidemic. From the eight case studies, it is concluded that family size, socio-economic status and some measure of good fortune in sustained good health enabled these people to live to an advanced age. While we recommend that targeted social protection is important in helping the poorest among the oldest, we suggest that sustaining respect for age and experience, and ensuring that older people do not feel discarded by family and society are as important as meeting their practical needs.
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    Vaginal Practices among Women at High Risk of HIV Infection in Uganda and Tanzania: Recorded Behaviour from a Daily Pictorial Diary
    (Claire Thorne, 2013) Francis, Suzanna C.; Baisley, Kathy; Lees, Shelley S.; Andrew, Bahati; Zalwango, Flavia; Seeley, Janet; Vandepitte, Judith.; T. Ao, Trong; van de Wijgert, Janneke; Watson-Jones, Deborah; Kapiga, Saidi; Grosskurth, Heiner; Hayes, Richard J.
    Background: Intravaginal practices (IVP) are highly prevalent in sub-Saharan African and have been implicated as risk factors for HIV acquisition. However, types of IVP vary between populations, and detailed information on IVP among women at risk for HIV in different populations is needed. We investigated IVP among women who practice transactional sex in two populations: semi-urban, facility workers in Tanzania who engage in opportunistic sex work; and urban, self-identified sex workers and bar workers in Uganda. The aim of the study was to describe and compare IVP using a daily pictorial diary. Methodology/Principal Findings: Two hundred women were recruited from a HIV prevention intervention feasibility study in Kampala, Uganda and in North-West Tanzania. Women were given diaries to record IVP daily for six weeks. Baseline data showed that Ugandan participants had more lifetime partners and transactional sex than Tanzanian participants. Results from the diary showed that 96% of Tanzanian participants and 100% of Ugandan participants reported intravaginal cleansing during the six week study period. The most common types of cleansing were with water only or water and soap. In both countries, intravaginal insertion (e.g. with herbs) was less common than cleansing, but insertion was practiced by more participants in Uganda (46%) than in Tanzania (10%). In Uganda, participants also reported more frequent sex, and more insertion related to sex. In both populations, cleansing was more often reported on days with reported sex and during menstruation, and in Uganda, when participants experienced vaginal discomfort. Participants were more likely to cleanse after sex if they reported no condom use. Conclusions: While intravaginal cleansing was commonly practiced in both cohorts, there was higher frequency of cleansing and insertion in Uganda. Differences in IVP were likely to reflect differences in sexual behaviour between populations, and may warrant different approaches to interventions targeting IVP. Vaginal practices among women at high risk in Uganda and Tanzania: recorded behaviour from a daily pictorial diary