Efficient regulatory approval of two novel HIV prevention interventions in a resource-limited setting: experiences from Zimbabwe

The global burden of HIV remains unacceptably high despite significant progress made in HIV treatment and prevention. There is an urgent need to scale up the comprehensive HIV prevention strategies that include pre-exposure prophylaxis (PrEP). Oral PrEP is highly effective in preventing HIV acquisition when taken regularly, but this remains a challenge for some at-risk individuals. Therefore, there is a need for other HIV prevention options. The dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA) are novel biomedical interventions that are safe and efficacious for HIV pre-exposure prophylaxis, as demonstrated in recently completed clinical trials. Timely roll-out and scalability of efficacious interventions depend on the registration process with the national medicine regulatory authorities (NMRAs). The Medicines Control Authority of Zimbabwe (MCAZ) was the first NMRA globally to approve the DVR in July 2021 and the first in Africa to approve CAB-LA for HIV prevention in July 2022. The regulatory review process for DVR and CAB-LA by MCAZ took 4.5 and 5.5 months, respectively. This efficient review process of the two interventions by MCAZ, a regulatory body in a resource-limited setting, provides important lessons to shorten timelines between the completion of the clinical development process and the registration of essential medicines

Survival of HIV Infected Children Born to Mothers Enrolled in a PMTCT Program in a Resource Poor Setting *

ABSTRACT Background: Pediatric HIV is a leading cause of morbidity and mortality worldwide. The substantial expansion in PMTCT has generated information on rates of transmission and associated factors, but there are limited studies on disease progression and mortality in vertically infected children, especially from resource poor settings. Methods: A birth cohort study was initiated in 2002 to focus on the role of a single dose of nevirapine in HIV transmission before Highly Active Antiretroviral Therapy (HAART) was readily available. The enrolment of women and subsequent follow up of the children occurred at 3 peri urban clinics around Harare. Findings: 479 women were HIV infected. From these, 93 (19%) children became HIV infected, 182 (38.0%) uninfected and 204 (43%) lost to follow up before HIV diagnosis. Of the HIV infected children, 40 (43%) died before the fifth birthday, 26 (28%) were lost to follow up and 27 (29%) were alive five years after maternal enrolment prior to availability of cART. Conclusion: In this setting, there was unacceptable high mortality from HIV infected children and loss to follow up prior to availability of HAART. A small proportion of HIV vertically infected children is surviving in resource poor settings without antiretroviral therapy

Sexual behaviour does not reflect HIV-1 prevalence differences: a comparison study of Zimbabwe and Tanzania

Background Substantial heterogeneity in HIV prevalence has been observed within sub-Saharan Africa. It is not clear which factors can explain these differences. Our aim was to identify risk factors that could explain the large differences in HIV-1 prevalence among pregnant women in Harare, Zimbabwe, and Moshi, Tanzania. Methods Cross-sectional data from a two-centre study that enrolled pregnant women in Harare (N = 691) and Moshi (N = 2654) was used. Consenting women were interviewed about their socio-demographic background and sexual behaviour, and tested for presence of sexually transmitted infections and reproductive tract infections. Prevalence distribution of risk factors for HIV acquisition and spread were compared between the two areas. Results The prevalence of HIV-1 among pregnant women was 26% in Zimbabwe and 7% in Tanzania. The HIV prevalence in both countries rises constantly with age up to the 25-30 year age group. After that, it continues to rise among Zimbabwean women, while it drops for Tanzanian women. Risky sexual behaviour was more prominent among Tanzanians than Zimbabweans. Mobility and such infections as HSV-2, trichomoniasis and bacterial vaginosis were more prevalent among Zimbabweans than Tanzanians. Reported male partner circumcision rates between the two countries were widely different, but the effect of male circumcision on HIV prevalence was not apparent within the populations. Conclusions The higher HIV-1 prevalence among pregnant women in Zimbabwe compared with Tanzania cannot be explained by differences in risky sexual behaviour: all risk factors tested for in our study were higher for Tanzania than Zimbabwe. Non-sexual transmission of HIV might have played an important role in variation of HIV prevalence. Male circumcision rates and mobility could contribute to the rate and extent of spread of HIV in the two countries

When are declines in condom use while using PrEP a concern? Modelling insights from a Hillbrow, South Africa case study.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is a promising new prevention approach for those most at risk of HIV infection. However, there are concerns that behavioural disinhibition, specifically reductions in condom use, might limit PrEP's protective effect. This study uses the case of female sex workers (FSWs) in Johannesburg, South Africa, to assess whether decreased levels of condom use following the introduction of PrEP may limit HIV risk reduction. METHOD: We developed a static model of HIV risk and compared HIV-risk estimates before and after the introduction of PrEP to determine the maximum tolerated reductions in condom use with regular partners and clients for HIV risk not to change. The model incorporated the effects of increased STI exposure owing to decreased condom use. Noting that condom use with regular partners is generally low, we also estimated the change in condom use tolerated with clients only, to still achieve 50 and 90% risk reduction on PrEP. The model was parameterized using data from Hillbrow, Johannesburg. Sensitivity analyses were performed to ascertain the robustness of our results. RESULTS: Reductions in condom use could be tolerated by FSWs with lower baseline condom use (65%). For scenarios where 75% PrEP effectiveness is attained, 50% HIV-risk reduction on PrEP would be possible even with 100% reduction in condom use from consistent condom use as high as 70% with clients. Increased exposure to STIs through reductions in condom use had limited effect on the reductions in condom use tolerated for HIV risk not to increase on PrEP. CONCLUSIONS: PrEP is likely to be of benefit in reducing HIV risk, even if reductions in condom use do occur. Efforts to promote consistent condom use will be critical for FSWs with high initial levels of condom use, but with challenges in adhering to PrEP

Type-Specific Cervico-Vaginal Human Papillomavirus Infection Increases Risk of HIV Acquisition Independent of Other Sexually Transmitted Infections

Sexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15) or HPV 70 (aHR 2.68; 95% CI 1.08-6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30), HPV 31 (aHR 4.25; 95% CI 1.81-9.97) or HPV 70 (aHR 3.30; 95% CI 1.50-7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21) or excluded (aHR 1.96; 95% CI 1.02-2.85) from the analysis.Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted

We chose PrEP because I wanted to be sure that this child my wife was going to conceive was indeed mine. Factors influencing the choice of safer conception methods and experiences with its use: a qualitative study among HIV sero-discordant couples in Zimbabwe.

BACKGROUND: Safer conception services are needed to minimize HIV transmission among HIV sero-discordant couples desiring pregnancy. Few studies have evaluated the choices couples make when they are offered multiple safer conception methods or real-world method acceptability. This paper addresses an important knowledge gap regarding factors that influence the choice of safer conception methods, couples actual experiences using safer conception methods, and why some couples switch safer conception methods. METHODS: Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples who exited the SAFER study-a pilot safer conception study for HIV sero-discordant couples in Zimbabwe that offered couples a choice of ART with monthly viral load monitoring (ART/VL), oral PrEP, vaginal insemination, and semen washing. All couples in SAFER had used at least two safer conception methods. RESULTS: We found that safer conception method choice often centered around a desire for intimacy, condomless sex, and certainty in the conception process, particularly for men. Method-related attributes such as familiarity, perceived ease of use, side effects, and perceived level of effectiveness in preventing HIV and achieving pregnancy influenced method choice, switching, and satisfaction. Concerns were expressed about each safer conception method and couples were willing to try different methods until they found method(s) that worked for them. The majority of participants reported having positive experiences using safer conception, especially those using ART/VL + PrEP, citing that they were able to attempt pregnancy for the first time with peace of mind and experienced joy and satisfaction from being able to achieve pregnancy safely. CONCLUSIONS: The differences in method preferences and experiences voiced by participants in this study and in other studies from the region point to the importance of having a variety of safer conception options in the service delivery package and addressing concerns about paternity, intimacy, and method-related attributes to enable HIV sero-discordant couples to safely achieve their reproductive goals

The burden and risk factors of Sexually Transmitted Infections and Reproductive Tract Infections among pregnant women in Zimbabwe

<p>Abstract</p> <p>Background</p> <p>Sexually transmitted infections (STIs) and Reproductive tract infections (RTIs) are responsible for high morbidity among women. We aim to quantify the magnitude of the burden and risk factors of STI/RTI s among pregnant women in Zimbabwe.</p> <p>Methods</p> <p>A cross sectional study of pregnant women enrolled at 36 weeks of gestation from the national PMTCT program. Study was conducted from three peri-urban clinics around Harare Zimbabwe offering maternal and child health services.</p> <p>Results</p> <p>A total of 691 pregnant women were enrolled. Prevalence of HSV was (51.1%), HIV (25.6%) syphilis (1.2%), <it>Trichomonas vaginalis </it>(11.8%), bacterial vaginosis (32.6%) and Candidiasis (39.9%). Seven percent of the women had genital warts, 3% had genital ulcers and 28% had an abnormal vaginal discharge. Prevalence of serological STIs and vaginal infections were 51% and 64% respectively.</p> <p>Risk factors for a positive serologic STI were increasing age above 30 years, polygamy and multigravid; adjusted OR (95% CI) 2.61(1.49-4.59), 2.16(1.06-4.39), 3.89(1.27-11.98) respectively, partner taking alcohol and number of lifetime sexual partners. For vaginal infections it was age at sexual debut; OR (95% CI) 1.60(1.06-2.42). More than 25% of the women reported previous STI treatment. Fifty two percent reported ever use of condoms and 65% were on oral contraceptives. Mean age gap for sexual partners was 6.3 years older.</p> <p>Conclusions</p> <p>There is a high morbidity of STI/RTIs in this cohort. There is need to continuously screen, counsel, treat and monitor trends of STI/RTIs to assess if behaviour changes lead to reduction in infections and their sustainability.</p

Human Immunodeficiency Virus (HIV) types Western blot (WB) band profiles as potential surrogate markers of HIV disease progression and predictors of vertical transmission in a cohort of infected but antiretroviral therapy naïve pregnant women in Harare, Zimbabwe

<p>Abstract</p> <p>Background</p> <p>Expensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression.</p> <p>Methods</p> <p>HIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV <it>gag </it>antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy.</p> <p>Results</p> <p>Among the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7%) had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants.</p> <p>Conclusion</p> <p>Absence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease diagnosis, WB test could also be used in conjunction with simpler tests like full blood counts and patient clinical assessment as a relatively cheaper disease monitoring tool required prior to accessing antiretroviral therapy for poor resource settings. However, there is also need to factor in the role of host-parasite genetics and interactions in disease progression.</p