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1.  Impact of Maternal and Infant Antiretroviral Drug Regimens on Drug Resistance in HIV-Infected Breastfeeding Infants 
The Pediatric infectious disease journal  2013;32(4):10.1097/INF.0b013e31827f44ee.
BACKGROUND
The HPTN 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV-infection despite prophylaxis.
METHODS
HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher’s exact tests were used to evaluate associations between categorical variables.
RESULTS
NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in seven (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8=75% in the NVP arm, 1/17=5.9% in the placebo arm, P=0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral (ARV) treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all four of those infants by 6 months of age (4/4=100%). In contrast, only three (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate ARV treatment developed NVP resistance (P=0.003).
CONCLUSIONS
Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.
doi:10.1097/INF.0b013e31827f44ee
PMCID: PMC3826537  PMID: 23249916
Nevirapine resistance; prevention of mother-to-child transmission; extended nevirapine; HIV
2.  Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial 
PLoS ONE  2013;8(11):e78818.
Background
Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment.
Methods and Findings
Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept.
Conclusions
In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.
doi:10.1371/journal.pone.0078818
PMCID: PMC3827276  PMID: 24236054
3.  Good Performance of Rapid Prostate-Specific Antigen Test for Detection of Semen Exposure in Women: Implications for Qualitative Research 
Sexually transmitted diseases  2009;36(8):501-506.
Background
Prostate-specific antigen (PSA) is a valid biomarker of semen exposure in women and has been used to assess reliability of self-reported sexual behavior as well as serve as a proxy measure for condom efficacy. Quantitative PSA tests are expensive and require specialized equipment. A simple, rapid, and inexpensive test for PSA would facilitate semen biomarker evaluation in a variety of research settings. This study evaluated the performance of a rapid PSA test compared with a quantitative assay to identify semen in vaginal swab specimens.
Methods
We tested 581 vaginal swabs collected from 492 women participating in 2 separate research studies in Bangladesh and Zimbabwe. PSA in vaginal secretions was detected using the quantitative IMx (Abbott Laboratories) assay and the ABAcard p30 (Abacus Diagnostics) rapid immunochromatographic strip test.
Results
The ABAcard test was 100% sensitive (95% confidence interval [CI], 98%–100%) and 96% specific (95% CI, 93%–97%) compared with the quantitative test in detecting >1.0 ng PSA/mL vaginal swab eluate. Rapid PSA results were semiquantitative and correlated well with PSA concentrations (κ = 0.88; 95% CI, 0.85–0.90).
Conclusion
Rapid PSA detection requires no instrumentation and can be performed easily and economically. Having rapid PSA results available immediately following interview provides opportunities to explore discrepancies between the objective marker of recent semen exposure and self-reported behaviors.
doi:10.1097/OLQ.0b013e3181a2b4bf
PMCID: PMC3790320  PMID: 19455082
4.  Willingness of Clinicians to Integrate Microbicides into HIV Prevention Practices in Southern Africa 
AIDS and behavior  2012;16(7):1821-1829.
The first vaginal microbicide was recently proven effective in clinical trials. We assessed the willingness of clinicians to integrate microbicides into HIV prevention practices in Southern Africa, where women face elevated HIV risks. We conducted in-depth interviews (n = 60) and nationally representative surveys (n = 1,444) in South Africa and Zimbabwe with nurses and physicians. Over half of clinicians (58%) were aware of microbicides, with physicians far more likely than nurses to be familiar. Clinicians, including those in rural areas, were generally willing to discuss microbicides, a female-initiated method less effective than the condom, particularly when condom use was unlikely (70%). Fewer would include microbicides while counseling adolescents (51%). Most clinicians (85%) thought their patients would use microbicides; greater clinician familiarity with microbicides was significant for support. Training for both nurses and physicians prior to introduction is critical, so they have sufficient knowledge and skills to offer a microbicide upon availability.
doi:10.1007/s10461-011-0109-6
PMCID: PMC3745300  PMID: 22210482
Microbicides; HIV prevention for women; Clinicians; Zimbabwe; South Africa
5.  Male Circumcision for HIV Prevention: Clinical Practices and Attitudes among Healthcare Providers in South Africa and Zimbabwe 
Sexually Transmitted Diseases  2012;39(7):567-575.
Background
This study aimed to document the clinical practices and attitudes of healthcare providers in South Africa and Zimbabwe on male circumcision for HIV prevention.
Methods
We conducted national surveys of physicians and nurses in both countries in 2008-2009 (N=1,444). Data on male circumcision for HIV prevention was analyzed; outcomes were patient counseling, provision of services, and desire for training. We used multivariable logistic regression to examine associations between these outcomes and clinician, practice and attitudinal variables.
Results
Overall, 57% of clinicians reported counseling male patients on male circumcision, 17% were offering services (49% referrals), and 61% desired training. In the multivariable analyses, provision of services was more common in South Africa (P≤.001), but desire for training higher in Zimbabwe (P≤.01). Provision of services was highest among physicians (p≤.01) and in hospital settings (P≤.001). However, nurses had greater desire for training (P≤.05) as did younger clinicians (P≤.001). Clinicians in rural and clinic settings were just as likely to express training interest. Clinician attitudes that patients would be upset due to cultural beliefs and would increase risky behaviors were associated with less counseling and service provision (P≤.05).
Conclusions
Many clinicians in South Africa and Zimbabwe showed willingness to integrate new HIV prevention evidence into practice and to become trained to offer the procedure to patients. Results suggest that both countries should consider involving nurses in male circumcision for HIV prevention, including those in rural areas, and should help clinicians to address cultural concerns.
doi:10.1097/OLQ.0b013e31824f9eaf
PMCID: PMC3377943  PMID: 22706221
Male circumcision; HIV prevention; Clinician practices; Zimbabwe; South Africa
6.  A nationally representative survey of healthcare provider counselling and provision of the female condom in South Africa and Zimbabwe 
BMJ Open  2013;3(3):e002208.
Objectives
Female condoms are the only female-initiated HIV and pregnancy prevention technology currently available. We examined female condom counselling and provision among providers in South Africa and Zimbabwe, high HIV-prevalence countries.
Design
A cross-sectional study using a nationally representative survey.
Setting
All facilities that provide family planning or HIV/sexually transmitted infection (STI) services.
Participants
National probability sample of 1444 nurses and physicians who provide family planning or HIV/STI services.
Primary and secondary outcome measures
Female condom practices with different female patients, including adolescents, married women, women using hormonal contraception and by HIV status. Using multivariable logistic analysis, we measured variations in condom counselling by provider characteristics.
Results
Most providers reported offering female condoms (88%; 1239/1415), but perceived a need for novel female barrier methods for HIV/STI prevention (85%; 1191/1396). By patient type, providers reported less frequent female condom counselling of adolescents (55%; 775/1411), women using hormonal contraception (65%; 909/1409) and married women (66%; 931/1416), compared to unmarried (74%; 1043/1414) or HIV-positive women (82%; 1161/1415). Multivariable results showed providers in South Africa were less likely to counsel women on female condoms than in Zimbabwe (OR=0.48, 95% CI 0.35 to 0.68, p≤0.001). However, South African providers were more likely to counsel women on male condoms (OR=2.39, 95% CI 1.57 to 3.65, p≤0.001). Nurses counselled patients on female condoms more frequently than physicians (OR=5.41, 95% CI 3.26 to 8.98, p≤0.001). HIV training, family planning training, location (urban vs rural) and facility type (hospital vs clinic) were not associated with greater condom counselling.
Conclusions
Female condoms were integrated into provider counselling and care, although providers reported a need for new female-initiated multipurpose prevention technologies, suggesting female condoms do not meet all patient/provider needs or are not adequately well known or accessible. Providers should be included in HIV training efforts to raise awareness of new and existing products, and encouraged to educate all women.
doi:10.1136/bmjopen-2012-002208
PMCID: PMC3612751  PMID: 23512836
7.  Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial 
Lancet  2011;379(9812):221-228.
Summary
Background
Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months.
Methods
In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primaryefficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412.
Findings
Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1.1% (95% CI 0.3–1.8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2.4% (1.3–3.6) of controls (difference 1.3%, 95% CI 0–2.6), equating to a 54% reduction in transmission (p=0.049). However, mortality (1.2% for nevirapine vs 1.1% for placebo; p=0.81) and combined HIV infection and mortality rates (2.3% vs 3.2%; p=0.27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups.
Interpretation
Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.
Funding
US National Institutes of Health.
doi:10.1016/S0140-6736(11)61653-X
PMCID: PMC3539769  PMID: 22196945
8.  Diaphragm Used with Replens Gel and Risk of Bacterial Vaginosis: Results from a Randomized Controlled Trial 
Background. Bacterial vaginosis (BV) has been linked to female HIV acquisition and transmission. We investigated the effect of providing a latex diaphragm with Replens and condoms compared to condom only on BV prevalence among participants enrolled in an HIV prevention trial. Methods. We enrolled HIV-seronegative women and obtained a vaginal swab for diagnosis of BV using Nugent's criteria; women with BV (score 7–10) were compared to those with intermediate (score 4–6) and normal flora (score 0–3). During quarterly follow-up visits over 12–24 months a vaginal Gram stain was obtained. The primary outcome was serial point prevalence of BV during followup. Results. 528 participants were enrolled; 213 (40%) had BV at enrollment. Overall, BV prevalence declined after enrollment in women with BV at baseline (OR = 0.4, 95% CI 0.29–.56) but did not differ by intervention group. In the intention-to-treat analysis BV prevalence did not differ between the intervention and control groups for women who had BV (OR = 1.01, 95% CI 0.52–1.94) or for those who did not have BV (OR = 1.21, 95% CI 0.65–2.27) at enrollment. Only 2.1% of participants were treated for symptomatic BV and few women (5–16%) were reported using anything else but water to cleanse the vagina over the course of the trial. Conclusions. Provision of the diaphragm, Replens, and condoms did not change the risk of BV in comparison to the provision of condoms alone.
doi:10.1155/2012/921519
PMCID: PMC3485870  PMID: 23133307
9.  HIV-1 Protease Inhibitors and Clinical Malaria: a Secondary Analysis of the AIDS Clinical Trials Group A5208 Study 
HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted.
doi:10.1128/AAC.05322-11
PMCID: PMC3264273  PMID: 22123685
10.  Nevirapine- Versus Lopinavir/Ritonavir-Based Initial Therapy for HIV-1 Infection among Women in Africa: A Randomized Trial 
PLoS Medicine  2012;9(6):e1001236.
In a randomized control trial, Shahin Lockman and colleagues compare nevirapine-based therapy with lopinavir/ritonavir-based therapy for HIV-infected women without previous exposure to antiretroviral treatment.
Background
Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.
Methods and Findings
In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm3 were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log10 below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm3, HIV RNA = 5.2 log10copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56–1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2–2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF.
Conclusions
Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm3.
Trial registration
ClinicalTrials.gov NCT00089505
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (mostly living in low- or middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of infection. Then, in 1996, antiretroviral therapy (ART)—cocktails of drugs that attack different parts of HIV—became available. For people living in affluent countries, HIV/AIDS became a chronic condition. But, because ART was expensive, for people living in developing countries, HIV/AIDS remained a fatal illness. In 2006, the international community set a target of achieving universal access to ART by 2010 and, although this target has not been reached, by the end of 2010, 6.6 million of the estimated 15 million people in need of ART in developing countries were receiving one of the ART regimens recommended by the World Health Organization (WHO) in its 2010 guidelines.
Why Was This Study Done?
A widely used combination for the initial treatment of HIV-infected people (particularly women) in resource-limited settings is tenofovir and emtricitabine (both nucleotide reverse transcriptase inhibitors; reverse transcriptase is essential for HIV replication) and nevirapine (NVP, a non-nucleoside reverse transcriptase inhibitor). However, little is known about the efficacy of this NVP-based ART combination. Moreover, its efficacy and toxicity has not been compared with regimens containing lopinavir/ritonavir (LPV/r). LPV/r, which inhibits the viral protease that is essential for HIV replication, is available in resource-limited settings but is usually reserved for second-line treatment. LPV/r-based ART is more expensive than NVP-based ART but if it were more effective or better tolerated than NVP-based ART, then first-line treatment with LPV/r-based ART might be cost-effective in resource-limited settings. Conversely, evidence of the clinical equivalence of NVP-based and LPV/r-based ART would provide support for NVP-based ART as an initial therapy. In this randomized equivalence trial, the researchers compare the efficacy and toxicity of NVP-based and LVP/r-based initial therapy for HIV infection among antiretroviral-naïve African women. In a randomized trial, patients are assigned different treatments by the play of chance and followed to compare the effects of these treatments; an equivalence trial asks whether the effects of two treatments are statistically equivalent.
What Did the Researchers Do and Find?
The researchers followed 500 antiretroviral-naïve HIV-infected women with a low CD4 cell count living in seven African countries, half of whom received NVP-based ART and half of whom received LPV/r-based ART, for an average of 118 weeks and recorded the time to virologic failure (the presence of virus in the blood above pre-specified levels) or death among the participants. Forty-two women in the NVP arm reached this primary endpoint (37 virologic failures and five deaths) compared to 50 women in the LPV/r arm (43 virologic failures and seven deaths), a result that indicates equivalent virologic efficacy according to preset statistical criteria. During the initial assigned treatment, similar proportions of women in both treatment arms developed serious drug-related signs and symptoms and laboratory abnormalities. However, whereas 14% of the women in the NVP arm discontinued treatment because of adverse effects, none of the women in the LPV/r arm discontinued treatment. Finally, nearly half of the women tested in the NVP arm but only 15% of the women tested in the LVP/r arm had developed any drug resistance at the time of virologic failure.
What Do These Findings Mean?
These findings indicate that, among HIV-infected, treatment-naïve African women, initial NVP-based ART is as effective as LPV/r-based ART in terms of virologic failure and death although more women in the NVP arm discontinued treatment or developed new drug resistance than in the LPV/r arm. Several limitations of this study may affect the accuracy of these findings. In particular, some of the study participants may have been exposed to single-dose NVP during childbirth to prevent mother-to-child transmission of HIV; in a parallel randomized trial, the researchers found that LPV/r-based ART was superior to NVP-based ART among women with prior exposure to single-dose NVP. Moreover, the duration of the current study means the long-term effects of the two treatments cannot be compared. Nevertheless, these findings support the WHO recommendation of NVP-based ART with careful early toxicity monitoring as an initial affordable and effective HIV treatment regiment in resource-limited settings, until access to better-tolerated and more potent regimens is possible.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001236.
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 charity on many aspects of HIV/AIDS, including detailed information on HIV treatment and care (in English and Spanish)
WHO provides information about universal access to AIDS treatment (in English, French and Spanish); its 2010 ART guidelines can be downloaded
More information about this trial, the OCTANE trial, is available
MedlinePlus provides detailed information about nevirapine and lopinavir/ritinovir (in English and Spanish)
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about taking anti-HIV drugs and the challenges of anti-HIV drugs
doi:10.1371/journal.pmed.1001236
PMCID: PMC3373629  PMID: 22719231
11.  Hormonal contraceptive use and HIV disease progression among women in Uganda and Zimbabwe 
Background
HIV-infected women need highly effective contraception to reduce unintended pregnancies and mother-to-child HIV transmission. Previous studies report conflicting results regarding the effect of hormonal contraception (HC) on HIV disease progression.
Methods
HIV-infected women in Uganda and Zimbabwe were recruited immediately after seroconversion; CD4 testing and clinical exams were conducted quarterly. The study endpoint was time to AIDS (two successive CD4 ≤200 cells/mm3 or WHO advanced stage 3 or stage 4 disease). We used marginal structural Cox survival models to estimate the effect of cumulative exposure to depot-medroxyprogesterone acetate (DMPA) and oral contraceptives (OC) on time to AIDS.
Results
303 HIV-infected women contributed 1,408 person-years (py). 111 women (37%) developed AIDS. Cumulative probability of AIDS was 50% at 7 years and did not vary by country. AIDS incidence was 6.6, 9.3 and 8.8 per 100py for DMPA, OC and non-hormonal users. Neither DMPA (adjusted hazard ratio (AHR) = 0.90; 95% CI 0.76-1.08) nor OCs (AHR =1.07; 95% CI 0.89-1.29) were associated with HIV disease progression. Alternative exposure definitions of HC use during the year prior to AIDS or at time of HIV infection produced similar results. STI symptoms were associated with faster progression while young age at HIV infection (18-24 years) was associated with slower progression. Adding baseline CD4 level and setpoint viral load to models did not change the HC results but subtype D infection became associated with disease progression.
Conclusion
Hormonal contraceptive use was not associated with more rapid HIV disease progression but older age, STI symptoms and subtype D infection were.
doi:10.1097/QAI.0b013e318214ba4a
PMCID: PMC3164299  PMID: 21358412
HIV; disease progression; hormonal contraception; family planning; women
12.  Increases in Human Papillomavirus Detection During Early HIV Infection Among Women in Zimbabwe 
The Journal of Infectious Diseases  2011;203(8):1182-1191.
Background. Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV).
Methods. One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes.
Results. We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models.
Conclusions. These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition.
doi:10.1093/infdis/jiq172
PMCID: PMC3068021  PMID: 21451006
13.  The Frequency of Malaria Is Similar among Women Receiving either Lopinavir/Ritonavir or Nevirapine-based Antiretroviral Treatment 
PLoS ONE  2012;7(4):e34399.
HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population.
doi:10.1371/journal.pone.0034399
PMCID: PMC3317955  PMID: 22509297
14.  Differences in HIV Natural History among African and Non-African Seroconverters in Europe and Seroconverters in Sub-Saharan Africa 
PLoS ONE  2012;7(3):e32369.
Introduction
It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations.
Methods
We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA.
Results
Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01).
Discussion
Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.
doi:10.1371/journal.pone.0032369
PMCID: PMC3295758  PMID: 22412867
15.  Investigating Potential Associations between Cervical Procedures and HIV Acquisition 
ISRN Obstetrics and Gynecology  2011;2011:789106.
Objective. Cervical human papillomavirus (HPV) infection has been associated with human immunodeficiency virus (HIV) acquisition in populations with a high prevalence of both infections. Procedures performed in the management of cervical dysplasia may facilitate HIV entry via mechanical injury. We sought to investigate the association between cervical procedures and incident HIV. Methods. Data on cervical cancer screening and procedures were collected in a cohort study evaluating the diaphragm for HIV prevention in 2040 women. In this secondary analysis, we investigated the association between cervical procedures and HIV acquisition. Results. Out of 2027 HIV-negative women at baseline, 199 underwent cervical procedures. Cumulative risk of HIV was 4.3% over 21 months of median followup (n = 88). Compared with women without cervical procedures, we observed no difference in HIV incidence after a cervical biopsy (RR 0.92, 95% CI 0.39–2.16), endocervical curettage (RR 0.29, 95% CI 0.07–1.22), or loop electrosurgical excision procedure (RR 1.00, 95% CI 0.30–3.30). Conclusions. In this cohort, cervical procedures were not associated with HIV incidence. This lack of association could be due to the small number of events.
doi:10.5402/2011/789106
PMCID: PMC3236408  PMID: 22191049
16.  Substantial Regional Differences in Human Herpesvirus 8 Seroprevalence in Sub-Saharan Africa: Insights on the Origin of the “KS Belt” 
Equatorial Africa has among the highest incidences of Kaposi’s sarcoma (KS) in the world, thus earning the name “KS Belt.” This was the case even prior to the HIV . To date, there is no clear evidence that HHV-8 seroprevalence is higher in this region, but interpretation of the available literature is tempered by differences in serologic assays used across studies. We examined representatively sampled ambulatory adults in Uganda, which is in the “KS Belt”, and in Zimbabwe and South Africa which are outside the Belt, for HHV-8 antibodies. All serologic assays were uniformly performed in the same reference laboratory by the same personnel. In the base-case serologic algorithm, seropositivity was defined by reactivity in an immunofluorescence assay or in two enzyme immunoassays. A total of 2375 participants were examined. In Uganda, HHV-8 seroprevalence was high early in adulthood (35.5% by age 21) without significant change thereafter. In contrast, HHV-8 seroprevalence early in adulthood was lower in Zimbabwe and South Africa (13.7% and 10.8%, respectively), but increased with age. After age adjustment, Ugandans had 3.24-fold greater odds of being HHV-8-infected than South Africans (p<0.001) and 2.22-fold greater odds than Zimbabweans (p<0.001). Inferences were unchanged using all other serologic algorithms evaluated. In conclusion, HHV-8 infection is substantially more common in Uganda than in Zimbabwe and South Africa. These findings help explain the high KS incidence in the “KS Belt” and underscore the importance of a uniform approach to HHV-8 antibody testing.
doi:10.1002/ijc.25235
PMCID: PMC2895015  PMID: 20143397
19.  Male circumcision and women's risk of incident chlamydial, gonococcal and trichomonal infections 
Sexually transmitted diseases  2008;35(7):689-695.
doi:10.1097/OLQ.0b013e31816b1fcc
PMCID: PMC2978019  PMID: 18418300
male circumcision; women; Chlamydia trachomatis; Neisseria gonorrhoeae; Trichomonas vaginalis
20.  Men's circumcision status and women's risk of HIV acquisition in Zimbabwe and Uganda 
AIDS (London, England)  2007;21(13):1779-1789.
doi:10.1097/QAD.0b013e32827b144c
PMCID: PMC2978032  PMID: 17690577
male circumcision; women; HIV; Zimbabwe; Uganda; misclassification
21.  Biomarker Validation of Reports of Recent Sexual Activity: Results of a Randomized Controlled Study in Zimbabwe 
American Journal of Epidemiology  2009;170(7):918-924.
Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006–2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fisher's exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.
doi:10.1093/aje/kwp219
PMCID: PMC3888136  PMID: 19741042
biological markers; condoms; data collection; epidemiologic measurements; HIV; prostate-specific antigen; sexual behavior
22.  The Importance of Male Partner Involvement for Women’s Acceptability and Adherence to Female-Initiated HIV Prevention Methods in Zimbabwe 
AIDS and Behavior  2010;15(5):959-969.
Enlisting male partner involvement is perceived as an important component of women’s successful uptake of female-initiated HIV prevention methods. We conducted a longitudinal study among a cohort of 955 Zimbabwean women participating in a clinical trial of the effectiveness of a female-initiated HIV prevention method (the diaphragm and lubricant gel) to: (a) describe the extent to which women involved their male partners in the decision to use the study products, and (b) measure the effect perceived male partner support had on their acceptability and consistent use of these methods. Reported levels of male partner involvement in discussions and decisions regarding: joining the study, study activities, the outcome of HIV/STI test results, and product use were very high. In multivariate analyses, regular disclosure of study product use and partner approval for the diaphragm and gel were significantly associated with women’s acceptability and consistent use of the products; an essential component for determining efficacy of investigational prevention methods. These results support the need for more sophisticated measurement of how couples interact to make decisions that impact study participation and investigational product use as well as more rigorous adaptations and evaluations of existing strategies to involve male partners in female-initiated HIV prevention trials.
doi:10.1007/s10461-010-9806-9
PMCID: PMC3111667  PMID: 20844946
HIV prevention; Female-initiated methods; Zimbabwe; Male involvement; Adherence; Acceptability; Couples
23.  Vaginal Practices of HIV-Negative Zimbabwean Women 
Background. Vaginal practices (VPs) may increase HIV risk by injuring vaginal epithelium or by increasing risk of bacterial vaginosis, an established risk factor for HIV. Methods. HIV-negative Zimbabwean women (n = 2,185) participating in a prospective study on hormonal contraception and HIV risk completed an ancillary questionnaire capturing detailed VP data at quarterly followup visits for two years. Results. Most participants (84%) reported ever cleansing inside the vagina, and at 40% of visits women reported drying the vagina using cloth or paper. Vaginal tightening using cloth/cotton wool, lemon juice, traditional herbs/powders, or other products was reported at 4% of visits. Women with ≥15 unprotected sex acts monthly had higher odds of cleansing (adjusted odds ratio (aOR): 1.17, 95% CI: 1.04–1.32). Women with sexually transmitted infections had higher odds of tightening (aOR: 1.42, 95% CI: 1.08–1.86). Conclusion. Because certain vaginal practices were associated with other HIV risk factors, synergism between VPs and other risk factors should be explored.
doi:10.1155/2010/387671
PMCID: PMC2943083  PMID: 20871844
24.  An acceptability and safety study of the Duet® cervical barrier and gel delivery system in Zimbabwe 
Background
Adherence problems with coitally dependent, female-initiated HIV prevention methods have contributed to several trials' failure to establish efficacy. Continuous use of a cervical barrier with once-daily cleaning and immediate reinsertion may simplify use for women and improve adherence. We assessed the acceptability and safety of precoital and continuous use of the Duet®, a cervical barrier and gel delivery system, in Zimbabwean women.
Methods
Using a two-arm crossover design with a parallel observation group, we randomized 103 women in a 2:2:1 ratio: (1) to use the Duet continuously for 14 days, followed by a minimum of seven days of washout and then 14 days of precoital use; (2) to use the same Duet regimens in reverse order; or (3) for observation only. Women were aged 18 to 40 years; half were recruited from a pool of previous diaphragm study participants and the other half from the general community. Acceptability and adherence were assessed through an interviewer-administered questionnaire at each of two follow-up visits. Safety was monitored through pelvic speculum exams and report of adverse events.
Results
The proportion of women who reported consistent Duet use during sex was virtually identical during continuous and precoital regimens (88.6% vs. 88.9%). Partner refusal was the most common reason cited for non-use during sex in both use regimens. Not having the device handy was the most common reason cited for non-daily use (in the continuous regimen). Most women were "very comfortable" using it continuously (86.3%) and inserting it precoitally (92.8%). The most favoured Duet attribute was that it did not interfere with "natural" sex (55%). The least favoured Duet attribute was the concern that it might come out during sex (71.3%). No serious adverse events were reported during the study; 57 participants reported 90 adverse events classified as mild or moderate. There were no statistically significant differences in: (1) the proportion of women reporting adverse events; (2) the severity of events among those using the Duet and observational controls; or (3) event severity reported during each regimen use period.
Conclusions
In this study, the Duet was found to be acceptable and safe when inserted precoitally or used continuously for 14 days. Assignment to use of the Duet continuously did not increase adherence to the Duet during sex. Future HIV prevention trials should evaluate use of the Duet (precoitally and continuously) with promising microbicide candidates.
doi:10.1186/1758-2652-13-30
PMCID: PMC2924266  PMID: 20687954
25.  Unprotected sex following HIV testing among women in Uganda and Zimbabwe: short- and long-term comparisons with pre-test behaviour 
Background Despite widespread condom promotion for HIV prevention, prospective measurement of condom use before and after HIV testing is infrequent.
Methods We analysed data from a prospective study of hormonal contraception and HIV acquisition among Zimbabwean and Ugandan women (1999–2004), in which HIV testing and counselling were performed approximately every 3 months. We used zero-inflated negative binomial (ZINB) models to examine the number and proportion of unprotected sex acts, comparing behaviour reported 2–6 months before HIV testing with behaviour reported both 2–6 months (short-term analysis) and 12–16 months (long-term analysis) after HIV testing.
Results Short- and long-term analyses were similar, so we present only long-term findings from 151 HIV-infected and 650 uninfected participants. The proportion of HIV-infected women reporting any unprotected acts in a typical month declined from 74% (pre-infection behaviour) to 56% (12–16 months after HIV diagnosis). In multivariable models, HIV-infected women were twice as likely to report that all sex acts were protected by condoms after diagnosis compared with beforehand [adjusted odds ratio (aOR): 1.99, 95% confidence interval (CI): 1.12–3.53]; uninfected women were somewhat less likely to report that all acts were protected (aOR: 0.82, 95% CI: 0.64–1.04). HIV-infected women also reduced their number of unprotected acts by 38% (95% CI: −16 to −55%). However, their proportion of unprotected acts changed little (7% reduction, 95% CI: −18 to + 6%). Uninfected women reported little change in number or proportion of unprotected acts over the same time period.
Conclusions HIV-infected women reduced the number, but not the proportion, of unprotected acts. HIV-negative women did not increase condom use after testing and counselling, but neither did they decrease condom use, suggesting that testing negative was not interpreted as endorsement of risky behaviour.
doi:10.1093/ije/dyp171
PMCID: PMC2720394  PMID: 19349481
Zero-inflated; negative binomial; HIV/AIDS; male condom; risk behaviour; positive prevention; women; Uganda; Zimbabwe; unprotected sex

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