Cheswa Vwalika

New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data

BACKGROUND Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV transmission within marriages, and HIV-prevention efforts remain focused on abstinence and non-marital sex. We aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year. METHODS We used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001-02 and in Rwanda in 2005. We also used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. We estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year. FINDINGS We analysed DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men. Under our base model, we estimated that 55.1% to 92.7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under our extended model, which incorporated the higher rates of reported condom use that we found with non-cohabiting partners, we estimated that 60.3% to 94.2% of new heterosexually acquired infections occurred within marriage or cohabitation. We estimated that an intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35.7% to 60.3% of heterosexually transmitted HIV infections that would otherwise occur. INTERPRETATION Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples.

Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa

ABSTRACT A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.

Effects of early, abrupt weaning on HIV-free survival of children in Zambia.

BACKGROUND In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. METHODS We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. RESULTS In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007). CONCLUSIONS Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.(ClinicalTrials.gov number, NCT00310726.)

Women in couples antenatal HIV counseling and testing are not more likely to report adverse social events

Background: Couple counseling has been promoted as a strategy to improve uptake of interventions to prevent mother-to-child HIV transmission (pMTCT) and to minimize adverse social outcomes associated with disclosure of HIV status. Objectives: We tested whether women counseled antenatally as part of a couple were more likely to accept HIV testing and nevirapine in a pMTCT program, and whether they would be less likely to experience later adverse social events than women counseled alone. Methods: A pMTCT program that included active community education and outreach to encourage couple counseling and testing was implemented in two antenatal clinics in Lusaka, Zambia. A subset of HIV-positive women was asked to report their experience of adverse social events 6 months after delivery. Couple-counseled women were compared with individual-counseled women stratified by whether or not they had disclosed their HIV status to their partners. Results: Nine percent (868) of 9409 women counseled antenatally were counseled with their husband. Couple-counseled women were more likely to accept HIV testing (96%) than women counseled alone (79%); however uptake of nevirapine was not improved. Six months after delivery, 28% of 324 HIV-positive women reported at least one adverse social event (including physical violence, verbal abuse, divorce or separation). There were no significant differences in reported adverse social events between couple- and individual-counseled women. Conclusions: Couple counseling did not increase the risk of adverse social events associated with HIV disclosure. Support services and interventions to improve social situations for people living with HIV need to be further evaluated.

High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission.

Background Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. Methods and Results As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. Conclusions Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their childrens lives. Trial Registration ClinicalTrials.gov NCT00310726

Predictors of nonadherence to single-dose nevirapine therapy for the prevention of mother-to-child HIV transmission.

Background:Adequate adherence is required for prevention of mother-to-child transmission of HIV (pMTCT) programs to be effective. We investigated predictors and extent of nonadherence to single-dose nevirapine. Methods:Data on nevirapine intake and possible predictors were collected among 760 HIV-positive women with liveborn babies enrolled in a study in Lusaka, Zambia. Results:Most (94%) women took nevirapine before delivery, and most (91%) newborns received it soon after delivery. Maternal nonadherence was associated with home births (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4), no high school education (OR: 2.4; 95% CI: 1.1 to 5.3), and low newborn birth weight (OR: 4.6; 95% CI: 1.3 to 20.1). Disclosure of HIV status and couples counseling was only associated with adherence among home births. Failure to administer nevirapine to the newborn was associated with birth at the tertiary hospital (OR: 7.2; 95% CI: 3.7 to 13.8), lower 5-minute Apgar scores (OR: 0.5; 95% CI: 0.4 to 0.7), and neonatal death (OR: 5.8; 95% CI: 2.0 to 16.3). Conclusions:Excellent adherence to single-dose nevirapine for pMTCT can be achieved. Nonadherence seems to be affected by place of birth and by poor health status of the newborn. Procedures to ensure that viable yet ill neonates receive nevirapine should be part of clinical protocols and training within pMTCT programs.

Promotion of couples' voluntary HIV counselling and testing in Lusaka, Zambia by influence network leaders and agents

Objectives Hypothesising that couples’ voluntary counselling and testing (CVCT) promotions can increase CVCT uptake, this study identified predictors of successful CVCT promotion in Lusaka, Zambia. Design Cohort study. Setting Lusaka, Zambia. Participants 68 influential network leaders (INLs) identified 320 agents (INAs) who delivered 29 119 CVCT invitations to heterosexual couples. Intervention The CVCT promotional model used INLs who identified INAs, who in turn conducted community-based promotion and distribution of CVCT invitations in two neighbourhoods over 18 months, with a mobile unit in one neighbourhood crossing over to the other mid-way through. Primary outcome The primary outcome of interest was couple testing (yes/no) after receipt of a CVCT invitation. INA, couple and invitation characteristics predictive of couples’ testing were evaluated accounting for two-level clustering. Results INAs delivered invitations resulting in 1727 couples testing (6% success rate). In multivariate analyses, INA characteristics significantly predictive of CVCT uptake included promoting in community-based (adjusted OR (aOR)=1.3; 95% CI 1.0 to 1.8) or health (aOR=1.5; 95% CI 1.2 to 2.0) networks versus private networks; being employed in the sales/service industry (aOR=1.5; 95% CI 1.0 to 2.1) versus unskilled manual labour; owning a home (aOR=0.7; 95% CI 0.6 to 0.9) versus not; and having tested for HIV with a partner (aOR=1.4; 95% CI 1.1 to 1.7) or alone (aOR=1.3; 95% CI 1.0 to 1.6) versus never having tested. Cohabiting couples were more likely to test (aOR=1.4; 95% CI 1.2 to 1.6) than non-cohabiting couples. Context characteristics predictive of CVCT uptake included inviting couples (aOR=1.2; 95% CI 1.0 to 1.4) versus individuals; the woman (aOR=1.6; 95% CI 1.2 to 2.2) or couple (aOR=1.4; 95% CI 1.0 to 1.8) initiating contact versus the INA; the couple being socially acquainted with the INA (aOR=1.6; 95% CI 1.4 to 1.9) versus having just met; home invitation delivery (aOR=1.3; 95% CI 1.1 to 1.5) versus elsewhere; and easy invitation delivery (aOR=1.8; 95% CI 1.4 to 2.2) versus difficult as reported by the INA. Conclusions This study demonstrated the ability of influential people to promote CVCT and identified agent, couple and context-level factors associated with CVCT uptake in Lusaka, Zambia. We encourage the development of CVCT promotions in other sub-Saharan African countries to support sustained CVCT dissemination.

A Randomized Controlled Trial to Promote Long-Term Contraceptive Use Among HIV-Serodiscordant and Concordant Positive Couples in Zambia.

BACKGROUND Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs). METHODS This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia. RESULTS Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods. CONCLUSIONS Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.

Prolonged breast-feeding and mortality up to two years post-partum among HIV-positive women in Zambia.

Background:A previously reported association between prolonged lactation and maternal mortality has generated concern that breast-feeding may be detrimental for HIV-positive women. Methods:As part of a trial conducted in Lusaka, Zambia, 653 HIV-positive women were randomly assigned either to a counseling program that encouraged abrupt cessation of breast-feeding at 4 months (group A) or to a program that encouraged prolonged breast-feeding for the duration of the womans own informed choice (group B). We examined whether mortality up to 2 years post-partum increased with breast-feeding for a longer duration. Results:There was no difference in mortality 12 months after delivery between 326 HIV-positive women randomly assigned to short breast-feeding [group A: 4.93%; 95% confidence interval (CI), 2.42–7.46] versus 327 women assigned to long breast-feeding (group B: 4.89%; 95% CI, 2.38–7.40). Analysis based on actual practice, rather than random assignment, also demonstrated no increased mortality due to breast-feeding. Conclusions:Although HIV-related mortality was high in this cohort of untreated HIV-positive women, prolonged lactation was not associated with increased mortality.

The Relationship Between Alcohol Consumption and Unprotected Sex Among Known HIV-discordant Couples in Rwanda and Zambia

Although alcohol abuse is highly prevalent in many countries in sub-Saharan Africa, little is known about the relationship between alcohol consumption and risky sexual behavior in these settings. An understanding of this relationship is particularly important given the high prevalence of HIV that exists in many of these countries. This study analyzes data collected from members of cohabiting HIV-discordant couples regarding alcohol consumption and self-reported condom use. After controlling for demographic and socioeconomic co-factors, alcohol use by male partners of HIV-discordant couples was associated with self-reported unprotected sex at follow-up. Counseling about alcohol use should be part of HIV testing and counseling programs, particularly among those found to be HIV-positive.