Search tips
Search criteria

Results 1-25 (39)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  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;182(7):633-643.
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.
PMCID: PMC4581589  PMID: 26316598
Africa; antiretroviral therapy; drug switching; dynamic marginal structural models; HIV; monitoring
2.  Safety of discontinuing cotrimoxazole prophylaxis among HIV infected adults on anti-retroviral therapy in Uganda (COSTOP trial): Design 
Contemporary Clinical Trials  2015;43:100-104.
Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design.
Materials and methods
COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm3 are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events.
Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations.
This paper describes the design and methodological considerations important for the conduct of CTX cessation studies.
PMCID: PMC4542218  PMID: 26009024
HIV infection; Cotrimoxazole prophylaxis; Stopping cotrimoxazole; Antiretroviral treatment; Cotrimoxazole cessation study design; Uganda
3.  High prevalence of hypertension and of risk factors for non-communicable diseases (NCDs): a population based cross-sectional survey of NCDS and HIV infection in Northwestern Tanzania and Southern Uganda 
BMC Medicine  2015;13:126.
The burden of non-communicable diseases (NCDs) is increasing in sub-Saharan Africa, but data available for intervention planning are inadequate. We determined the prevalence of selected NCDs and HIV infection, and NCD risk factors in northwestern Tanzania and southern Uganda.
A population-based cross-sectional survey was conducted, enrolling households using multistage sampling with five strata per country (one municipality, two towns, two rural areas). Consenting adults (≥18 years) were interviewed using the WHO STEPS survey instrument, examined, and tested for HIV and diabetes mellitus (DM). Adjusting for survey design, we estimated population prevalences of hypertension, DM, obstructive pulmonary disease, cardiac failure, epilepsy and HIV, and investigated factors associated with hypertension using logistic regression.
Across strata, hypertension prevalence ranged from 16 % (95 % confidence interval (CI): 12 % to 22 %) to 17 % (CI: 14 % to 22 %) in Tanzania, and from 19 % (CI: 14 % to 26 %) to 26 % (CI: 23 % to 30 %) in Uganda. It was high in both urban and rural areas, affecting many young participants. The prevalence of DM (1 % to 4 %) and other NCDs was generally low. HIV prevalence ranged from 6 % to 10 % in Tanzania, and 6 % to 12 % in Uganda. Current smoking was reported by 12 % to 23 % of men in different strata, and 1 % to 3 % of women. Problem drinking (defined by Alcohol Use Disorder Identification Test criteria) affected 6 % to 15 % men and 1 % to 6 % women. Up to 46 % of participants were overweight, affecting women more than men and urban more than rural areas. Most patients with hypertension and other NCDs were unaware of their condition, and hypertension in treated patients was mostly uncontrolled. Hypertension was associated with older age, male sex, being divorced/widowed, lower education, higher BMI and, inversely, with smoking.
The high prevalence of NCD risk factors and unrecognized and untreated hypertension represent major problems. The low prevalence of DM and other preventable NCDs provides an opportunity for prevention. HIV prevalence was in line with national data. In Tanzania, Uganda and probably elsewhere in Africa, major efforts are needed to strengthen health services for the PREVENTION, early detection and treatment of chronic diseases.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0357-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4476208  PMID: 26021319
Non-communicable diseases; hypertension; diabetes mellitus; heart failure; obstructive pulmonary disease; HIV infection; NCD risk factors; WHO STEPS survey; Africa
4.  Association between Mycoplasma genitalium infection and HIV acquisition among female sex workers in Uganda: evidence from a nested case–control study 
Sexually Transmitted Infections  2014;90(7):545-549.
Cross-sectional studies have shown a strong association between Mycoplasma genitalium and HIV infections. We previously reported that in a cohort of female sex workers in Uganda, M genitalium infection at baseline was associated with HIV seroconversion. Here we examine the temporal association between the M genitalium infection status shortly before HIV seroconversion and HIV acquisition.
A nested case-control study was conducted within a cohort of women at high risk for HIV in Kampala. Cases were those of women acquiring HIV within 2 years of enrolment. For each of the 42 cases, 3 controls were selected from women HIV negative at the visit when the corresponding case first tested HIV seropositive. The association between HIV acquisition and M genitalium infection immediately prior to HIV testing was analysed using conditional logistic regression.
There was weak evidence of an association between M genitalium infection and HIV acquisition overall (crude OR=1.57; 95% CI 0.67 to 3.72, aOR=2.28: 95% CI 0.81 to 6.47). However, time of M genitalium testing affected the association (p value for effect-modification=0.004). For 29 case-control sets with endocervical samples tested 3 months prior to the first HIV-positive result, M genitalium infection increased the risk of HIV acquisition (crude OR=3.09; 95% CI 1.06 to 9.05, aOR=7.19; 95% CI 1.68 to 30.77), whereas there was little evidence of an association among the 13 case-control sets with samples tested at an earlier visit (crude OR=0.30: 95% CI 0.04 to 2.51; aOR=0.34; 95% CI 0.02 to 5.94).
Our study showed evidence of a temporal relationship between M genitalium infection and HIV acquisition that suggests that M genitalium infection may be a co-factor in the acquisition of HIV infection.
PMCID: PMC4215342  PMID: 24687129
5.  Short Communication: HIV Type 1 Transmitted Drug Resistance and Evidence of Transmission Clusters Among Recently Infected Antiretroviral-Naive Individuals from Ugandan Fishing Communities of Lake Victoria 
Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the fishing communities on Lake Victoria in Uganda are high. This population may play a role in driving the HIV epidemic in Uganda including the spread of transmitted drug resistance (TDR). We report data on TDR in this population among antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV scaling-up in Uganda. We identified phylogenetic transmission clusters and combined these with volunteer life histories in order to understand the sexual networks within this population. From a prospective cohort of 1,000 HIV-negative individuals recruited from five communities, 51 seroconverters were identified over a period of 2 years. From these, whole blood was collected and population sequencing of the HIV-1 pol gene (protease/reverse transcriptase) was performed from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list for surveillance of TDR. TDR prevalence categories were estimated using the WHO recommended truncated sampling technique for the surveillance of TDR for use in resource-limited settings (RLS). Of the samples 92% (47/51) were successfully genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47 (2%) C, 1/47 (2%) G, and 10/47 (21%) unique recombinant forms. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. No nucleoside/tide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we identified five transmission clusters supported by high bootstrap values and low genetic distances. Of these, one pair included the two individuals with K103N. Two of the genotypic clusters corresponded with reported sexual partnerships as detected through prior in-depth interviews. The level of TDR to NNRTIs in these ARV-naive individuals was moderate by WHO threshold survey categorization. The transmission clusters suggest a high degree of sexual partner mixing between members of these communities.
PMCID: PMC3636596  PMID: 23173702
6.  Preparedness of Tanzanian health facilities for outpatient primary care of hypertension and diabetes: a cross-sectional survey 
The Lancet Global Health  2014;2(5):e285-e292.
Historically, health facilities in sub-Saharan Africa have mainly managed acute, infectious diseases. Few data exist for the preparedness of African health facilities to handle the growing epidemic of chronic, non-communicable diseases (NCDs). We assessed the burden of NCDs in health facilities in northwestern Tanzania and investigated the strengths of the health system and areas for improvement with regard to primary care management of selected NCDs.
Between November, 2012, and May, 2013, we undertook a cross-sectional survey of a representative sample of 24 public and not-for-profit health facilities in urban and rural Tanzania (four hospitals, eight health centres, and 12 dispensaries). We did structured interviews of facility managers, inspected resources, and administered self-completed questionnaires to 335 health-care workers. We focused on hypertension, diabetes, and HIV (for comparison). Our key study outcomes related to service provision, availability of guidelines and supplies, management and training systems, and preparedness of human resources.
Of adult outpatient visits to hospitals, 58% were for chronic diseases compared with 20% at health centres, and 13% at dispensaries. In many facilities, guidelines, diagnostic equipment, and first-line drug therapy for the primary care of NCDs were inadequate, and management, training, and reporting systems were weak. Services for HIV accounted for most chronic disease visits and seemed stronger than did services for NCDs. Ten (42%) facilities had guidelines for HIV whereas three (13%) facilities did for NCDs. 261 (78%) health workers showed fair knowledge of HIV, whereas 198 (59%) did for hypertension and 187 (56%) did for diabetes. Generally, health systems were weaker in lower-level facilities. Front-line health-care workers (such as non-medical-doctor clinicians and nurses) did not have knowledge and experience of NCDs. For example, only 74 (49%) of 150 nurses had at least fair knowledge of diabetes care compared with 85 (57%) of 150 for hyptertension and 119 (79%) of 150 for HIV, and only 31 (21%) of 150 had seen more than five patients with diabetes in the past 3 months compared with 50 (33%) of 150 for hypertension and 111 (74%) of 150 for HIV.
Most outpatient services for NCDs in Tanzania are provided at hospitals, despite present policies stating that health centres and dispensaries should provide such services. We identified crucial weaknesses (and strengths) in health systems that should be considered to improve primary care for NCDs in Africa and identified ways that HIV programmes could serve as a model and structural platform for these improvements.
UK Medical Research Council.
PMCID: PMC4013553  PMID: 24818084
7.  Natural history of Mycoplasma genitalium Infection in a Cohort of Female Sex Workers in Kampala, Uganda 
Sexually transmitted diseases  2013;40(5):422-427.
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.
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.
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 HIV-negative 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.
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.
PMCID: PMC3928562  PMID: 23588134
8.  Quantitative and Qualitative Differences in the T Cell Response to HIV in Uninfected Ugandans Exposed or Unexposed to HIV-Infected Partners 
Journal of Virology  2013;87(16):9053-9063.
HIV-exposed and yet persistently uninfected individuals have been an intriguing, repeated observation in multiple studies, but uncertainty persists on the significance and implications of this in devising protective strategies against HIV. We carried out a cross-sectional analysis of exposed uninfected partners in a Ugandan cohort of heterosexual serodiscordant couples (37.5% antiretroviral therapy naive) comparing their T cell responses to HIV peptides with those of unexposed uninfected individuals. We used an objective definition of exposure and inclusion criteria, blinded ex vivo and cultured gamma interferon (IFN-γ) enzyme-linked immunospot assays, and multiparameter flow cytometry and intracellular cytokine staining to investigate the features of the HIV-specific response in exposed versus unexposed uninfected individuals. A response rate to HIV was detectable in unexposed uninfected (5.7%, 95% confidence interval [CI] = 3.3 to 8.1%) and, at a significantly higher level (12.5%, 95% CI = 9.7 to 15.4%, P = 0.0004), in exposed uninfected individuals. The response rate to Gag was significantly higher in exposed uninfected (10/50 [20.%]) compared to unexposed uninfected (1/35 [2.9%]) individuals (P = 0.0004). The magnitude of responses was also greater in exposed uninfected individuals but not statistically significant. The average number of peptide pools recognized was significantly higher in exposed uninfected subjects than in unexposed uninfected subjects (1.21 versus 0.47; P = 0.0106). The proportion of multifunctional responses was different in the two groups, with a higher proportion of single cytokine responses, mostly IFN-γ, in unexposed uninfected individuals compared to exposed uninfected individuals. Our findings demonstrate both quantitative and qualitative differences in T cell reactivity to HIV between HESN (HIV exposed seronegative) and HUSN (HIV unexposed seronegative) subject groups but do not discriminate as to whether they represent markers of exposure or of protection against HIV infection.
PMCID: PMC3754030  PMID: 23760253
9.  Is hypertension the new HIV epidemic? 
PMCID: PMC3937981  PMID: 24491955
10.  Vaginal practices diary: development of a pictorial data collection tool for sensitive behavioural data 
Sexually transmitted diseases  2012;39(8):10.1097/OLQ.0b013e3182515fe4.
Intravaginal practices (IVP) are highly prevalent behaviours among women at increased risk for HIV in sub-Saharan Africa. IVP data collected by face-to-face interviews (FTFI) may be subject to recall or social desirability bias. Daily self-administered diaries may help to decrease bias associated with FTFI. IVP data from a diary and FTFI were compared during a multi-site microbicide feasibility study in Tanzania and Uganda.
Two hundred women were recruited and given diaries to complete daily for six weeks. Data obtained in the diary were compared to data from the FTFI during clinical visits to assess the consistency of reporting of IVP between the data collection methods.
In Tanzania, proportions of overall vaginal cleansing and insertion were similar for the FTFI and the diary, but the diary indicated higher frequency of cleansing and use of a cloth or other applicator. In Uganda, proportions of overall vaginal cleansing were similar for FTFI and the diary, but the diary indicated higher frequency of cleansing, use of soaps and cloths for cleansing, and insertion. Most of the inconsistencies between the two data collection methods were from reported frequency of IVP or IVP related to sexual intercourse.
The comparison of FTFI and the vaginal practice diary suggests that recall of IVP may be improved by a daily self-administered diary, especially for frequency of cleansing and cleansing in proximity to sexual intercourse. The vaginal practices diary can provide a more detailed understanding of IVP and aid in the interpretation of findings from FTFI. Vaginal practices diary: development of a pictorial data collection tool for sensitive behavioural data.
PMCID: PMC3827744  PMID: 22801344
Vaginal practices; Diary; HIV; Sexual behaviour; sub-Saharan Africa
11.  Difference in blood pressure response to ACE-Inhibitor monotherapy between black and white adults with arterial hypertension: a meta-analysis of 13 clinical trials 
BMC Nephrology  2013;14:201.
Among African-Americans adults, arterial hypertension is both more prevalent and associated with more complications than among white adults. Hypertension is also epidemic among black adults in sub-Saharan Africa. The treatment of hypertension among black adults may be complicated by lesser response to certain classes of anti-hypertensive agents.
We systematically searched literature for clinical trials of ACE-inhibitors among hypertensive adults comparing blood pressure response between whites and blacks. Meta-analysis was performed to determine the difference in systolic and diastolic blood pressure response. Further analysis including meta-regressions, funnel plots, and one-study-removed analyses were performed to investigate possible sources of heterogeneity or bias.
In a meta-analysis of 13 trials providing 17 different patient groups for evaluation, black race was associated with a lesser reduction in systolic (mean difference: 4.6 mmHg (95% CI 3.5-5.7)) and diastolic (mean difference: 2.8 mmHg (95% CI 2.2-3.5)) blood pressure response to ACE-inhibitors, with little heterogeneity. Meta-regression revealed only ACE-inhibitor dosage as a significant source of heterogeneity. There was little evidence of publication bias.
Black race is consistently associated with a clinically significant lesser reduction in both systolic and diastolic blood pressure to ACE-inhibitor therapy in clinical trials in the USA and Europe. In black adults requiring monotherapy for uncomplicated hypertension, drugs other than ACE-inhibitors may be preferred, though the proven benefits of ACE-inhibitors in some sub-groups and the large overlap of response between blacks and whites must be remembered. These data are particularly important for interpretation of clinical drug trials for hypertensive black adults in sub-Saharan Africa and for the development of treatment recommendations in this population.
PMCID: PMC3849838  PMID: 24067062
Blood pressure; Hypertension; Treatment; ACE-inhibitors; Race; Black; White; Meta-analysis
12.  Effect of HIV-1 Subtypes on Disease Progression in Rural Uganda: A Prospective Clinical Cohort Study 
PLoS ONE  2013;8(8):e71768.
We examined the association of HIV-1 subtypes with disease progression based on three viral gene regions.
A prospective HIV-1 clinical cohort study in rural Uganda.
Partial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment.
Between 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR), (95% CI) = 1.72 (1.16–2.54), but this was mainly due to events in the period before antiretroviral therapy (ART) introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI) = 1.78 (1.01–3.14).
In this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes.
PMCID: PMC3741119  PMID: 23951241
13.  Alcohol use, Mycoplasma genitalium and other STIs associated with HIV incidence among women at high risk in Kampala, Uganda 
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.
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.
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%).
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.
PMCID: PMC3529920  PMID: 23075920
HIV incidence; Mycoplasma genitalium; STIs; alcohol; women at high risk; risk factors; Uganda
14.  Vaginal Practices among Women at High Risk of HIV Infection in Uganda and Tanzania: Recorded Behaviour from a Daily Pictorial Diary 
PLoS ONE  2013;8(3):e59085.
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.
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.
PMCID: PMC3608607  PMID: 23555618
15.  A Single CD4 Test with 250 Cells/Mm3 Threshold Predicts Viral Suppression in HIV-Infected Adults Failing First-Line Therapy by Clinical Criteria 
PLoS ONE  2013;8(2):e57580.
In low-income countries, viral load (VL) monitoring of antiretroviral therapy (ART) is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable.
3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded) or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s) in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4<100 cells/mm3) were reviewed in 361 LCM, 314 CDM participants who switched over median 5 years follow-up. Retrospective VLs were available in 368 (55%) participants.
Overall, 265/361 (73%) LCM participants failed with CD4<100 cells/mm3; only 7 (2%) switched with CD4≥250 cells/mm3, four switches triggered by WHO events. Without CD4 monitoring, 207/314 (66%) CDM participants failed with WHO 4 events, and 77(25%)/30(10%) with single/multiple WHO 3 events. Failure/switching with single WHO 3 events was more likely with CD4≥250 cells/mm3 (28/77; 36%) (p = 0.0002). CD4 monitoring reduced switching with viral suppression: 23/187 (12%) LCM versus 49/181 (27%) CDM had VL<400 copies/ml at failure/switch (p<0.0001). Amongst CDM participants with CD4<250 cells/mm3 only 11/133 (8%) had VL<400copies/ml, compared with 38/48 (79%) with CD4≥250 cells/mm3 (p<0.0001).
Multiple, but not single, WHO 3 events predicted first-line ART failure. A CD4 threshold ‘tiebreaker’ of ≥250 cells/mm3 for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 ‘clinical failures’ would particularly avoid premature, costly switch to second-line ART.
PMCID: PMC3578828  PMID: 23437399
16.  HIV-1 Transmission within Marriage in Rural Uganda: A Longitudinal Study 
PLoS ONE  2013;8(2):e55060.
Early initiation of antiretroviral therapy reduces risk of transmission to the uninfected partner in HIV discordant couples, but there are relatively little observational data on HIV transmission within couples from non-trial settings. The aims of this paper are to estimate HIV incidence among HIV discordant couples using longstanding observational data from a rural Ugandan population and to identify factors associated with HIV transmission within couples, including the role of HSV-2 infection.
Using existing data collected at population-wide annual serological and behavioural surveys in a rural district in southwest Uganda between 1989 and 2007, HIV discordant partners were identified. Stored serum samples were tested for HSV-2 serostatus using the Kalon ELISA test. HIV seroconversion rates and factors association with HIV seroconversion were analysed using Poisson regression.
HIV status of both partners was known in 2465 couples and of these 259 (10.5%) were HIV serodiscordant. At enrolment, HSV-2 prevalence was 87.3% in HIV positive partners and 71.5% in HIV negative partners. Of the 259 discordant couples, 62 converted to HIV (seroconversion rate 7.11/100 PYAR, 95%CI; 5.54, 9.11) with the rate decreasing from 10.89 in 1990–1994 to 4.32 in 2005–2007. Factors independently associated with HIV seroconversion were female sex, non-Muslim religion, greater age difference (man older than woman by more than 15 years), higher viral load in the positive partner and earlier calendar period. HSV-2 was not independently associated with HIV acquisition (HR 1.62, 95%CI; 0.57, 4.55) or transmission (HR 0.61, 95%CI; 0.24, 1.57). No transmissions occurred in the 29 couples where the index partner was on ART during follow up (872 person-years on ART).
HIV negative partners in serodiscordant couples have a high incidence of HIV if the index partner is not on antiretroviral therapy and should be provided with interventions such as couple counselling, condoms and antiretroviral treatment.
PMCID: PMC3563659  PMID: 23390512
17.  Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial 
PLoS Medicine  2012;9(5):e1001217.
Diana Gibb and colleagues investigate the effect of in utero tenofovir exposure by analyzing the pregnancy and infant outcomes of HIV-infected women enrolled in the DART trial.
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.
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.
Trial registration ISRCTN13968779
Please see later in the article for the Editors' Summary
Editors' Summary
Currently, about 34 million people (mostly in low- and middle-income countries) are infected with HIV, the virus that causes AIDS. At the beginning of the epidemic, more men than women were infected with HIV but now about half of all people living with HIV/AIDS are women, most of who became infected through unprotected sex with an infected partner. In sub-Saharan Africa alone, 12 million women are HIV-positive. Worldwide, HIV/AIDS is the leading cause of death among women of child-bearing age. Moreover, most of the 400,000 children who become infected with HIV every year acquire the virus from their mother during pregnancy or birth, or through breastfeeding, so-called mother-to-child transmission (MTCT). Combination antiretroviral therapy (ART)—treatment with cocktails of powerful antiretroviral drugs—reduces HIV-related illness and death among women, and ART given to HIV-positive mothers during pregnancy and delivery and to their newborn babies greatly reduces MTCT.
Why Was This Study Done?
Because of ongoing international efforts to increase ART coverage, more HIV-positive women in Africa have access to ART now than ever before. However, little is known about pregnancy outcomes among HIV-infected African women taking ART throughout pregnancy for their own health or about the long-term outcomes of their offspring. In particular, few studies have examined the effect of taking tenofovir (an antiretroviral drug that is now recommended as part of first-line ART) throughout pregnancy. Tenofovir readily crosses from mother to child during pregnancy and, in animal experiments, high doses of tenofovir given during pregnancy caused bone demineralization (which weakens bones), kidney problems, and impaired growth among offspring. In this study, the researchers analyze data collected on pregnancy and infant outcomes among Ugandan and Zimbabwean HIV-positive women who took ART throughout pregnancy in the Development of AntiRetroviral Therapy in Africa (DART) trial. This trial was designed to test whether ART could be safely and effectively delivered in Africa without access to the expensive laboratory tests that are routinely used to monitor ART toxicity and efficacy in developed countries.
What Did the Researchers Do and Find?
The pregnancy outcomes of 302 women who became pregnant during the DART trial and information on birth defects among their babies were collected as part of the DART protocol; information on the survival, growth, and development of the infants born to these women was collected in a separate infant study. Most of the women who became pregnant were taking tenofovir-containing ART before and throughout their pregnancies. 58% of the pregnancies resulted in a live birth, 7% resulted in a stillbirth (birth of a dead baby at any time from 22 weeks gestation to the end of pregnancy), and 35% resulted in a termination or miscarriage (before 22 weeks gestation). Of the 226 live births, seven infants died within 2 weeks and seven had birth defects. Similar proportions of the infants exposed and not exposed to tenofovir during pregnancy died soon after birth or had birth defects. Of the 182 surviving infants who were enrolled in the infant study, 14 subsequently died at an average age of 9 months, giving a 1-year mortality of 5%. None of the surviving children who were tested (172 infants) were HIV infected. No bone fractures or major kidney problems occurred during follow-up and prebirth exposure to tenofovir in utero had no effect on growth or weight gain at 2 years (in contrast to a previous US study).
What Do These Findings Mean?
By showing that prebirth tenofovir exposure does not affect pregnancy outcomes or increase birth defects, growth abnormalities, or kidney problems, these findings support the use of tenofovir-containing ART during pregnancy among HIV-positive African women, and suggest that it could also be used to prevent women of child-bearing age acquiring HIV-infection heterosexually. Notably, the observed 5% 1-year infant mortality is similar to the 2%–4% infant mortality normally seen in the region. The absence of HIV infection among the infants born to the DART participants is also encouraging. However, this is a small study (only 111 infants were exposed to tenofovir throughout pregnancy) and women were not randomly assigned to receive tenofovir-containing ART. Consequently, more studies are needed to confirm that tenofovir exposure during pregnancy does not affect pregnancy outcomes or have any long-term effects on infants. Such studies are essential because the use of tenofovir as a treatment for women who are HIV-positive is likely to increase and tenofovir may also be used in the future to prevent HIV acquisition in HIV-uninfected women.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment (in several languages)
Information is available from Avert, an international AIDS nonprofit on many aspects of HIV/AIDS, including detailed information on HIV/AIDS treatment and care, women, HIV and AIDS, children, HIV and AIDS, and on HIV/AIDS and pregnancy (some information in English and Spanish); personal stories of women living with HIV are available
More information about the DART trial is available
Additional patient stories about living with HIV/AIDS are available through the nonprofit website Healthtalkonline
PMCID: PMC3352861  PMID: 22615543
18.  Cost Effectiveness Analysis of Clinically Driven versus Routine Laboratory Monitoring of Antiretroviral Therapy in Uganda and Zimbabwe 
PLoS ONE  2012;7(4):e33672.
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.
PMCID: PMC3335836  PMID: 22545079
19.  Distribution of hyperglycaemia and related cardiovascular disease risk factors in low-income countries: a cross-sectional population-based survey in rural Uganda 
Background Data on non-communicable disease (NCD) burden are often limited in developing countries in Africa but crucial for planning and implementation of prevention and control strategies. We assessed the prevalence of related cardiovascular disease risk factors (hyperglycaemia, high blood pressure and obesity) in a longstanding population cohort in rural Uganda.
Methods Trained field staff conducted a cross-sectional population-based survey of cardiovascular disease risk indicators using a questionnaire and simple measurements of body mass index (BMI), waist and hip circumference, waist/hip ratio (WHR), blood pressure and random plasma glucose. All members of the population cohort aged ≥13 years were eligible to participate in the survey.
Results Of the 4801 males and 5372 females who were eligible, 2719 (56.6%) males and 3959 (73.7%) females participated in the survey. Male and female participants had a mean standard deviation (SD) age of 31.8 (18.4) years and 33.7 (17.6) years, respectively. The observed prevalences of probable diabetes (glucose >11.0 mmol/l) and probable hyperglycaemia (7.0–11.0 mmol/l) were 0.4 and 2.9%, respectively. Less than 1% of males and 4% of females were obese (BMI ≥30 kg/m2), with 3.6% of males and 14.5% of females being overweight (BMI 25.0–29.9 kg/m2). However, in women, the prevalence of abdominal obesity was high (71.3% as measured by WHR and 31.2% as measured by waist circumference). The proportions of male and female current regular smokers were low (13.7 and 0.9%, respectively). The commonest cardiovascular disease risk factor was high blood pressure, with an observed prevalence of 22.5% in both sexes.
Conclusions Population-based data on the burden of related cardiovascular disease risk factors can aid in the planning and implementation of an effective response to the double burden of communicable diseases and NCDs in this rural population of a low-income country undergoing epidemiological transition.
PMCID: PMC3043279  PMID: 20926371
Cardiovascular disease; prevalence; Africa
20.  Health and functional status among older people with HIV/AIDS in Uganda 
BMC Public Health  2011;11:886.
In sub-Saharan Africa, little is known about the health and functional status of older people who either themselves are HIV infected or are affected by HIV and AIDS in the family. This aim of this study was to describe health among older people in association with the HIV epidemic.
The cross-sectional survey consisted of 510 participants aged 50 years and older, equally divided into five study groups including; 1) HIV infected and on antiretroviral therapy (ART) for at least 1 year; 2) HIV infected and not yet eligible for ART; 3) older people who had lost a child due to HIV/AIDS; 4) older people who have an adult child with HIV/AIDS; 5) older people not known to be infected or affected by HIV in the family. The participants were randomly selected from ongoing studies in a rural and peri-urban area in Uganda. Data were collected using a WHO standard questionnaire and performance tests. Eight indicators of health and functioning were examined in an age-adjusted bivariate and multivariate analyses.
In total, 198 men and 312 women participated. The overall mean age was 65.8 and 64.5 years for men and women respectively. Men had better self-reported health and functional status than women, as well as lower self-reported prevalence of chronic diseases. In general, health problems were common: 35% of respondents were diagnosed with at least one of the five chronic conditions, including 15% with depression, based on algorithms; 31% of men and 35% of women had measured hypertension; 25% of men and 21% of women had poor vision test results. HIV-positive older people, irrespective of being on ART, and HIV-negative older people in the other study groups had very similar results for most health status and functioning indicators. The main difference was a significantly lower BMI among HIV-infected older people.
The systematic exploration of health and well being among older people, using eight self-reported and objective health indicators, showed that basic health problems are very common at older ages and poorly addressed by existing health services. HIV-infected older people, however, whether on ART or not yet on ART, had a similar health and functional status as other older people.
PMCID: PMC3256234  PMID: 22111659
21.  Mortality in an antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study 
There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions.
Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses.
1453 subjects were enrolled with baseline median count of 108 cells/μl. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first year and 2.4 (1.8, 3.2) deaths thereafter. The one, two and three year survival probabilities (95% CI) were 0.89 (0.87 - 0.91), 0.86 (0.84 - 0.88) and 0.85 (0.83 - 0.87) respectively. Low baseline CD4 count, low body weight, advanced clinical condition (WHO stages III and IV), not being on cotrimoxazole prophylaxis and male gender were associated independently with increased mortality. Tuberculosis, cryptococcal meningitis and diarrhoeal disease were estimated to be major causes of death.
Practical and affordable interventions are needed to enable earlier initiation of ART and to reduce mortality risk among those who present late for treatment with advanced disease.
PMCID: PMC3210087  PMID: 22018282
Antiretroviral therapy; HIV; Africa; survival; cause of death; adult; Uganda; health care delivery
22.  HIV Incidence and Risk Factors for Acquisition in HIV Discordant Couples in Masaka, Uganda: An HIV Vaccine Preparedness Study 
PLoS ONE  2011;6(8):e24037.
To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.
HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.
495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1–6]; and 4.3 [2.8–6.4] and 4.4 [2.5–8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18–24 (aRR = 4.1, 95% CI 1.6–10.8) and 25–34 (aRR = 2.7, 95% CI 1.2–5.8) years]; alcohol use (aRR = 2.6, 95% CI 1.1–6); and reported genital discharge (aRR = 3.4, 95% CI 1.6–7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2–0.8); always (aRR = 0.1, 95% CI 0.02–0.9)]. In the follow-up risk analysis, young age [18–24 (aRR = 6.2, 95% CI 2.2–17.3) and 25-34 (aRR = 2.3, 95% CI 1.1–5.0) years], reported genital discharge (aRR = 2.5, 95% CI 1.1–5.5), serological syphilis (aRR 3.2, 95% CI 1.3–7.7) and the partner being ART naïve (aRR = 4.8, 95% CI 1.4–16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.
The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population.
PMCID: PMC3166075  PMID: 21909379
23.  Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans 
PLoS ONE  2011;6(5):e19902.
The use of cellular coreceptors and modulation of cytokine concentrations by HIV to establish a productive infection is well documented. However, it is unknown whether the expression of these proteins affects the course of HIV clade A and D disease, reported to have different progression rates.
Methodology/Principal Findings
We investigated whether the number of CD4+ T-cells expressing CCR5 or CXCR4, the density of these coreceptors and concentrations of specific immune proteins linked to HIV pathogenesis vary between individuals infected with HIV clade A or D. We undertook additional analyses stratifying participants by early (CD4>500 cells/µl) or late (CD4<200 cells/µl) disease stage. Whole blood samples were taken from 50 HIV-1 infected individuals drawn from cohorts in rural south-west Uganda. Late stage participants had less than half the number of CD4+/CCR5+ T-cells (p = 0.0113) and 5.6 times fewer CD4+/CXCR4+ cells (p<0.0001) than early stage participants. There was also a statistically significant difference in the density of CXCR4 on CD4+ cells between clade A and D infected early stage participants (142 [A] vs 84 [D]; p = 0.0146). Across all participants we observed significantly higher concentration of Th1 cytokines compared to Th2 (66.4 vs 23.8 pg/ml; p<0.0001). Plasma concentrations of IFNγ and IL-2 were 1.8 and 2.4 fold lower respectively in Late-D infected participants compared to Late-A participants. MIP-1β levels also decreased from 118.0 pg/ml to 47.1 pg/ml (p = 0.0396) as HIV disease progressed.
We observed specific alterations in the abundance of CD4+/CCR5+ and CD4+/CXCR4+ T-cells, and concentrations of immune proteins across different HIV clades and as infection progresses. Our results suggest that these changes are unlikely to explain the observed differences in disease progression between subtype A and D infections. However, our observations further the understanding of the natural progression of non-clade B HIV infection and how the virus adapts to exploit the host environment.
PMCID: PMC3104992  PMID: 21655330
24.  Multiple HIV-1 infections with evidence of recombination in heterosexual partnerships in a low risk Rural Clinical Cohort in Uganda 
Virology  2011;411(1):113-131.
We report on the frequency of multiple infections, generation of recombinants and consequences on disease progression in 35 HIV-1 infected individuals from 7 monogamous and 6 polygamous partnerships within a Rural Clinical Cohort in Uganda. The env-C2V3, gag-p24 and pol-IN genes were sequenced. Single genome amplified half genome sequences were used to map recombination breakpoints. Three participants were dually infected with subtypes A and D, one case with subtype A and A/D recombinant and the fifth with 2 phylogenetically distinct A/D recombinants. Occurrence of A/D recombination was observed in two multiple infected individuals. Rate of late stage WHO events using Cox regression was 3 times greater amongst multiple infected compared to singly infected individuals (hazard ratio 3.35; 95% CI 1.09, 10.3; p = 0.049). We have shown that polygamous relationships involving subtype discordant partnerships was a major contributor of multiple infections with generation of inter subtype recombinants in our cohort.
PMCID: PMC3041926  PMID: 21239033
HIV-1; Multiple infections; Superinfection; Coinfection; Recombination
25.  CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy 
AIDS Research and Treatment  2011;2011:875028.
Objective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed. Methods. CD8+ T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths, and functionality of IFN-γ and Perforin responses were compared in STI (n = 42) and continuous treatment (CT) (n = 46) before and after a single STI cycle when the DART STI trial was stopped early due to inferior clinical outcome in STI participants. Results. STI and CT had comparable magnitudes and breadths of monofunctional CD8+IFNγ+ and CD8+Perforin+ responses. However, STI was associated with significant decline in breadth of bi-functional (CD8+IFNγ+Perforin+) responses; P = .02, Mann-Whitney test. Conclusions. STI in individuals initiated onto ART at <200 CD4+ T-cell counts/μl significantly reduced occurrence of bifunctional CD8+IFNγ+/Perforin+ responses. These data add to others that found no evidence to support STI as a strategy to improve HIV-specific immunity during ART.
PMCID: PMC3065901  PMID: 21490785

Results 1-25 (39)